title: The Role of Viral Infection in Pulmonary Exacerbations of Bronchiectasis in Adults A Prospective Study

text: BACKGROUND Although viral infections are a major cause of exacerbations in patients with chronic airway diseases, their roles in triggering bronchiectasis exacerbations in adults remain unclear. Therefore, we prospectively investigated the incidence and clinical impacts of viral infection in adults with bronchiectasis exacerbations. METHODS The study cohort of 119 adults with bronchiectasis was followed up prospectively for 12 months. Nasopharyngeal swabs and sputum samples were assayed for 16 respiratory viruses, using polymerase chain reaction assays. Symptoms, spirometry, quality of life, bacterial cultures, and inflammatory markers were assessed during steady-state bronchiectasis and exacerbations. RESULTS A total of 100 exacerbations were captured from 58 patients during 1-year follow-up. Respiratory viruses were found more frequently in nasopharyngeal swabs and sputum during bronchiectasis exacerbations (49 of 100, 49.0') than during steady state (11 of 58, 18.9'; P < .001). The most common viruses found in patients experiencing exacerbations were coronavirus (19 of 65, 39.2'), rhinovirus (16 of 65, 24.6'), and influenza A/B viruses (16 of 65, 24.6'). Virus-positive exacerbations were associated with a greater increase in markers of systemic and airway inflammation (serum IL-6 and tumor necrosis factor-α; sputum IL-1β and tumor necrosis factor-α) compared with virus-negative exacerbations, but the differences in spirometric indexes, quality of life, and bacterial density were unremarkable. In receiver operating characteristics analysis, serum interferon-γ-induced protein 10 yielded an area under curve of 0.67 (95' CI, 0.53-0.77; P = .018). Furthermore, a greater proportion of patients with virus-positive exacerbations received IV antibiotics. CONCLUSIONS Prevalence of viral infections, detected by polymerase chain reaction assay, is higher in cases of bronchiectasis exacerbations than in steady-state bronchiectasis, suggesting that respiratory viruses play crucial roles in triggering bronchiectasis exacerbations. The potential mechanisms of virus-induced bronchiectasis exacerbations merit further investigations. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01801657; www.clinicaltrials.gov


docid: qcihtlor

title: Control of an Outbreak of Human Parainfluenza Virus 3 in Hematopoietic Stem Cell Transplant Recipients

text: Human parainfluenza virus 3 (HPIV3) infection can cause significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). There are no standard guidelines for the prevention and control of HPIV3 in the outpatient setting. After 2 HSCT inpatients diagnosed with HPIV3 were noted to have had multiple recent HSCT outpatient clinic (OPC) visits, an investigation of policy and procedures in the HSCT OPC was undertaken, and active surveillance for respiratory viral illness was instituted in the at-risk HSCT population. Between July 19 and August 30, 2005, 13 patients were diagnosed with HPIV3 infection. Morbidity in affected patients was significant, and mortality was high (38.5%) and not affected by antiviral therapy. Molecular typing identified several genetically distinct groups of the hemagglutinin-neuraminidase gene of the 11 available isolates. Based on sequence relatedness among the isolates and the demographic and exposure history of the patients, in many of these cases HPIV3 infection likely was acquired in the HSCT OPC. The major infection control interventions were introduced between August 20 and August 24. An epidemic curve revealed that HPIV3 infection frequency peaked between August 17 and August 26, with no cases identified after August 30. Prompt attention and focus on infection control interventions were associated with a rapid decrease in the number of incident cases. Policies and procedures regarding patients with respiratory viral illnesses in HSCT OPC populations should be formulated and universally reinforced with HSCT clinic staff to prevent the spread of these infections.


title: Identifying agents triggering bronchiolitis in the State of Qatar

text: BACKGROUND: Bronchiolitis is considered as the most frequent lower respiratory tract infection in infants and young children. This disorder is marked by acute inflammation, edema, damage of epithelial cells lining small airways, and augmentation of mucus production. OBJECTIVE: The goal of the study was to identify agents triggering bronchiolitis in the State of Qatar. MATERIALS AND METHODS: A cross-sectional retrospective study was performed at Hamad Medical Corporation, the only tertiary and academic medical center in the State of Qatar. The study included infants and young children aged 0–24 months who were admitted to our pediatric ward with diagnosis of acute bronchiolitis (2010–2012) RESULTS: Eight hundred thirty-five infants and young children met the study inclusion criteria with mean age at diagnosis of 3.61±3.56 months. Respiratory virus real-time polymerase chain reaction was performed on 769 (92.0%) of the participants. Respiratory syncytial virus (RSV) was positive in 352 (45.7%) children admitted with clinical bronchiolitis. In addition, no viruses were identified in 142 (18.4%) of those admitted, and respiratory viruses other RSV were found in 275 (35.7%) of the children. Our investigations and observations show that there has been a steady and periodic seasonal variation in the RSV rate over the study period. A seasonal trend for the RSV (detected by respiratory virus real-time polymerase chain reaction) rate was evident, showing annual peaks in the months of October, November, December, and January, with a significant test for seasonality (test statistics [T]=3.15, P=0.009). CONCLUSION: In countries with desert hot weather, bronchiolitis might affect children throughout the year. Our results suggest that the combination of date regarding uninterrupted RSV seasonality can provide guidance for health care planning and application of RSV prevention scheme, such as extending the palivizumab immunoglobulin series.


Mental Health, Physical Activity, and Quality of Life in Parkinson's Disease During COVID‐19 Pandemic


The myth of masks: a tale of risk selection in the COVID‐19 pandemic


COVID-19: ONCE UPON A TIME IN PORTUGAL A brief atlas of ongoing pandemic Portuguese research


title: Intestinal transplantation during COVID‐19 pandemic

text: With the wide spread of the COVID‐19 in the world, all activities related to health care have been affected and this includes transplantation surgeries (1). Considering the high transmission rate of the virus and limitations in resources such as intensive care unit (ICU) beds and blood products, in many countries living donor transplantations and pancreas transplantation have been delayed to after the diseases has subsided.


title: False‐negative of RT‐PCR and prolonged nucleic acid conversion in COVID‐19: Rather than recurrence

text: A novel coronavirus (COVID‐19) pandemic cause by Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) threatens the world. We read with interest the recent report by Li et al. that included 610 patients with Coronavirus Disease 2019 (COVID‐19). They reported a high false‐negative rate of real‐time reverse transcription polymerase chain reaction (RT‐PCR) results for SARS‐CoV‐2 detection. In addition, recent report regarding SARS‐CoV‐2 “turn positive” in recovered cases with COVID‐19 were published. Here, we studied the characteristics of nucleic acid conversion for SARS‐CoV‐2 from 70 COVID‐19 patients. We found that 15 (21.4%) patients experienced a “turn positive” of nucleic acid detection by RT‐PCR test for SARS‐CoV‐2 after two consecutive negative results, which may be related to the false negative of RT‐PCR test and prolonged nucleic acid conversion This article is protected by copyright. All rights reserved.


title: Respiratory viral infections in pregnant women with asthma are associated with wheezing in the first 12 months of life

text: BACKGROUND: There are few studies investigating the relationship between respiratory viral infection in pregnancy and asthma in the offspring, and none among mothers with asthma. Infants of mothers with asthma are more likely to wheeze and have a higher risk of developing asthma than infants of non‐asthmatic mothers. METHODS: A prospective cohort study of viral infection in pregnancy was conducted between 2007 and 2009, and a subgroup of infants of mothers with asthma was followed up at 6 and 12 months of age. During common colds, nasal and throat swabs were collected from mothers and respiratory viruses detected by polymerase chain reaction. Respiratory health of infants was assessed by parent‐completed questionnaire. RESULTS: Twelve‐month‐old infants whose mothers had confirmed viral infections in pregnancy (n = 26) reported more frequent wheeze (40% had 4–12 wheeze attacks compared with 0%), sleep disturbed by wheeze (1 night per week or more in 60% vs. 11%), beta agonist treatment for wheeze (27% vs. 0%), prolonged colds (2 wk or longer 31% vs. 0%), more eczema (40% vs. 6.3%), and parent‐perceived asthma (32% vs. 0%), compared with infants whose mothers had common colds without laboratory‐confirmed viral infection (n = 16). CONCLUSIONS: This study demonstrates a relationship between maternal respiratory viral infection in pregnancy and wheezing illness in infants of mothers with asthma. Viral infections are the most common cause of asthma exacerbations in pregnancy, and infants of asthmatic mothers are at increased risk of asthma themselves. Further research is needed to elucidate the mechanisms involved.


docid: mnafslqw

title: Fetal exposure to herpesviruses may be associated with pregnancy‐induced hypertensive disorders and preterm birth in a Caucasian population

text: Objective To investigate the role of fetal viral infection in the development of a range of adverse pregnancy outcomes (APOs), including pregnancy‐induced hypertensive disorders (PIHD), antepartum haemorrhage (APH), birthweight <10th percentile (small for gestational age, SGA) and preterm birth (PTB). Design Population‐based case–control study. Setting Laboratory‐based study. Population The newborn screening cards of 717 adverse pregnancy cases and 609 controls. Methods Newborn screening cards were tested for RNA from enteroviruses and DNA from herpesviruses using polymerase chain reaction (PCR). The herpesviruses were detected using two PCRs, one detecting nucleic acids from herpes simplex virus (HSV)‐1, HSV‐2, Epstein–Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus (HHV)‐8, hereafter designated Herpes PCR group A viruses, and the other detecting nucleic acids from varicella‐zoster virus (VZV), HHV‐6 and HHV‐7, hereafter designated Herpes PCR group B viruses. Main outcome measure Odds ratios and 95% CIs for specific APOs. Results For both term and PTBs, the risk of developing PIHD was increased in the presence of DNA from Herpes PCR group B viruses (OR 3.57, 95% CI 1.10–11.70), CMV (OR 3.89, 95% CI 1.67–9.06), any herpesvirus (OR 5.70, 95% CI 1.85–17.57) and any virus (OR 5.17, 95% CI 1.68–15.94). The presence of CMV was associated with PTB (OR 1.61, 95% CI 1.14–2.27). No significant association was observed between SGA or APH and exposure to viral infection. Conclusions Fetal exposure to herpesvirus infection was associated with PIHD for both term and PTBs in this exploratory study. Exposure to CMV may also be associated with PTB. These findings need confirmation in future studies.


title: The Challenges and Opportunities for Shared Decision Making Highlighted by COVID-19

text: Abstract Shared decision making (SDM) is a management paradigm that empowers patients as partners in their own care in a bidirectional exchange of information and values, and optimize the decision-making process. During the current COVID-19 pandemic, there is a greater need to encourage participation in the SDM process. The pandemic has created both challenges and opportunities for delivering care, as system adaptations influence the physician-patient relationship. While social distancing and health service reallocation can interfere with preference for an in-person visit, these measures also provide an avenue to study and implement virtual SDM processes. Communicating risk at a time of heightened uncertainty may pose a barrier to SDM engagement but provides the opportunity to foster a patient-centered approach within a more personalized context. Social media influence during COVID-19 has resulted in an ‘infodemic’ but highlights the importance of patient engagement. The pandemic has changed how we deliver care but allows us to re-evaluate common practices and enhance effectiveness of our management strategies. Navigating the uncertainty of subsequent pandemic waves creates confusion about how to safely reinitiate clinical service. This will require ongoing SDM with our patients and amongst colleagues through current—and future—challenges. COVID-19 has created many difficulties but has forced us to re-examine how to provide more patient-centered and high-quality care.


title: Ancient pathogen genomics as an emerging tool for infectious disease research

text: Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA, enabling complete genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. In this Review, we discuss methodological advancements, persistent challenges and novel revelations gained through the study of ancient pathogen genomes.


docid: lzdwpaki

title: Combination of Biodata Mining and Computational Modelling in Identification and Characterization of ORF1ab Polyprotein of SARS-CoV-2 Isolated from Oronasopharynx of an Iranian Patient

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging zoonotic viral infection, which was started in Wuhan, China, in December 2019 and transmitted to other countries worldwide as a pandemic outbreak. Iran is one of the top ranked countries in the tables of COVID-19-infected and -mortality cases that make the Iranian patients as the potential targets for diversity of studies including epidemiology, biomedical, biodata, and viral proteins computational modelling studies. RESULTS: In this study, we applied bioinformatic biodata mining methods to detect CDS and protein sequences of ORF1ab polyprotein of SARS-CoV-2 isolated from oronasopharynx of an Iranian patient. Then through the computational modelling and antigenicity prediction approaches, the identified polyprotein sequence was analyzed. The results revealed that the identified ORF1ab polyprotein belongs to a part of nonstructural protein 1 (nsp1) with the high antigenicity residues in a glycine-proline or hydrophobic amino acid rich domain. CONCLUSIONS: The results revealed that nsp1 as a virulence factor and crucial agent in spreading of the COVID-19 among the society can be a potential target for the future epidemiology, drug, and vaccine studies.


title: WU polyomavirus detected in children with severe respiratory failure

text: Abstract Background WU polyomavirus (WUPyV) is a relatively new virus associated with respiratory infections. However, its role is unclear in children with severe respiratory failure. Objectives We aimed to evaluate the characteristics of severe respiratory failure associated with WUPyV infection in children. Study design We retrospectively reviewed cases of respiratory tract infection at a tertiary children's hospital in Japan and performed real-time polymerase chain reaction (PCR) for WUPyV using residual extracted nucleic acid samples taken from respiratory tract samples of pediatric patients primarily with respiratory failure. We investigated the clinical characteristics of patients positive for WUPyV and assessed samples positive for WUPyV for other respiratory pathogens using multiplex PCR. Results WUPyV was detected in 14 of 318 specimens of respiratory tract infections. The median age was 34 months and males were predominant (n = 11, 64%). An underlying disease was found in 11 (79%) patients including five preterm and three immunocompromised patients. The most common clinical diagnosis was pneumonia (n = 13, 93%). The majority of the samples were endotracheal tube aspirates (n = 11, 79%). Other viruses were co-detected in nine (64%) patients, while WUPyV was the only pathogen detected in five patients with a history of admission to the neonatal intensive care unit. These five patients presented with fever and cough, and perihilar infiltrates were detected on chest radiograph in several days. Conclusions WUPyV was detected in children with severe respiratory failure independently or concurrently with other pathogens. WUPyV can be a pathogen for children with a history of preterm birth or an underlying disease.


title: COVID-19: molecular diagnostics overview

text: The last day of 2019 delivered the first report to the World Health Organization (WHO) about a group of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified the new comer, a novel coronavirus related to severe acute respiratory syndrome coronavirus (SARS-CoV) and thus was termed as SARS-CoV-2. Being very contagious, the new virus led the era of “COVID-19” which is the acronym of “coronavirus disease 2019,” evoking an imminent threat to global health security with unprecedented devastating challenges to human kind. In this article, we provide a molecular overview on the SARS-CoV-2 virus and summarize tremendous efforts that have been made to develop a rapid confirmatory diagnostic test for COVID-19. The diagnostic performances of the available tests are analyzed based on the best current information from the early research.


title: Epidemic Assistance by the Epidemic Intelligence Service, Centers for Disease Control and Prevention, 2005–2014

text: BACKGROUND: Epi-Aids, or epidemiologic assistance investigations, are an important mechanism through which Centers for Disease Control and Prevention supports public health organizations. We described the characteristics of Epi-Aids conducted during 2005–2014 and summarized the publication outcome of Epi-Aid related scientific information products. METHODS: We performed a descriptive analysis of all Epi-Aids conducted during January 1, 2005–December 31, 2014; investigations were categorized by health topic and geographic distribution. We highlighted investigations of substantial public health importance, e.g., multistate investigations and investigations of epidemics and pandemics. We identified the Epi-Aid publication outcome by searching PubMed for Epi-Aid related publications, which included Morbidity and Mortality Weekly Reports (MMWRs) and peer-reviewed publications with an Epidemic Intelligence Service Officer (EISO) as a coauthor. We calculated publication timeliness and categorized publications by journal impact factor. RESULTS: During the study period, 698 EISOs and their collaborators participated in 807 Epi-Aids throughout the United States and globally. Approximately 81 Epi-Aids were conducted annually (range, 62–104); 632 (78.3%) were infectious disease-related; 161 (20.0%) were international, supporting 68 countries. As of June 2015, EISOs, in collaboration with partners, published 131 MMWRs and 280 scientific manuscripts on the basis of the 807 Epi-Aids conducted during the study period; 394 (48.8%) Epi-Aids resulted in publications in 80 peer-reviewed journals. CONCLUSIONS: EISOs play a critical role in conducting Epi-Aids, which require qualified field epidemiologists who can rapidly respond to requests for assistance during public health emergencies. Publications based on Epi-Aids share new knowledge with the scientific community, furthering progress of public health science and practice.


docid: gioqkeda

title: Climate Change and the Geographic Distribution of Infectious Diseases

text: Our ability to predict the effects of climate change on the spread of infectious diseases is in its infancy. Numerous, and in some cases conflicting, predictions have been developed, principally based on models of biological processes or mapping of current and historical disease statistics. Current debates on whether climate change, relative to socioeconomic determinants, will be a major influence on human disease distributions are useful to help identify research needs but are probably artificially polarized. We have at least identified many of the critical geophysical constraints, transport opportunities, biotic requirements for some disease systems, and some of the socioeconomic factors that govern the process of migration and establishment of parasites and pathogens. Furthermore, we are beginning to develop a mechanistic understanding of many of these variables at specific sites. Better predictive understanding will emerge in the coming years from analyses regarding how these variables interact with each other.


G6PD deficiency‐associated hemolysis and methemoglobinemia in a COVID‐19 patient treated with chloroquine


title: Evaluation of bacteriophage efficacy in reducing the impact of single and mixed infections with Escherichia coli and infectious bronchitis in chickens

text: Infectious bronchitis virus (IBV) represents a major threat to poultry production worldwide particularly when complicated with bacterial infection. In the present study samples were collected from forty broiler farms with respiratory manifestations to characterize IBV and E. coli. Bacteriophages were isolated and enriched from sampled farms to study its efficacy to control single and mixed infections with E. coli and IBV in vivo. Twelve out of forty farms were positive for IBV. Phylogenetic analysis of partial spike protein revealed that all positive cases clustered within the GI-23 genotype. Eight out of forty farms were positive for E. coli serogroups O26, O78, O86, O114, O119, with O125 found on three farms. Bacteriophage treatment delayed the onset and reduced the severity of clinical signs, and prevented the mortality associated with single and mixed infection with IBV and E. coli. Furthermore, in mixed infections, bacteriophage treatment significantly reduced E. coli as well as IBV shedding. Groups treated with bacteriophages showed a significant reduction of E. coli shedding that gradually decreased over time, in contrast to higher and gradually increasing shedding without bacteriophage treatment. In conclusion, bacteriophage treatment significantly reduced the pathogenicity and shedding of IBVand E. coli in mixed infections.


title: Why Racial Justice Matters in Radiation Oncology

text: Recent events have reaffirmed that racism is a pervasive disease plaguing the United States, infiltrating the fabric of this nation. As healthcare professionals dedicated to understanding and alleviating disease, many radiation oncologists have failed to acknowledge how structural racism impacts the health and well-being of the patients we aim to serve. The literature is full of descriptive statistics showing the higher incidence and mortality experienced by Blacks for health conditions ranging from infant mortality to infectious disease, including COVID19. Acknowledgement that the root of health disparities experienced by Blacks in this country is based in racism is essential to moving the nation and the field of radiation oncology forward. With this lens, a brief overview of structural and institutional racism shapes a discussion of what radiation oncologists and the organizations that represent them can do to address this scourge. As members of a technological field, we often harness the power of data to advance human health and approach challenging diseases with optimism that multidisciplinary effort can produce cure. A few principles to mitigate the longstanding issues of Black marginalization within the field have been recommended, via the ATIP and LEADS approaches. However, additional introspection is encouraged. Just as individuals, practices and organizations rallied to determine how best to address the issues related to the COVID19 pandemic, the same investigational fervor must be applied to the issue of racism in order to combat this sinister and often deadly disease.


The Case for a Temporary COVID-19 Income Tax Levy Now, During the Crisis


title: Chapter 16 Bacterial Diseases

text: Abstract Common marmosets are susceptible to a number of bacterial infections, which may be enzootic, causing sporadic but occasionally severe disease, or which may result in epizootics associated with more severe colony morbidity and mortality. The spectrum of these diseases often differs from those observed in macaque species, and veterinarians caring for common marmosets need to be aware of these unique susceptibilities. In formulating differential diagnoses for sick or diseased animals, it should be recognized that diseases once common in imported animals in the 1960s and 1970s are now rare. It is also important to recognize that housing and sanitation conditions can influence exposure to potentially pathogenic bacteria. In a zoological setting where mixed- or free-ranging exhibits are utilized, animals may be exposed to many more potential pathogens than would be the case in animals raised in a barrier facility.


title: Differentiated cultures of primary hamster tracheal airway epithelial cells

text: Primary airway epithelial cell cultures can provide a faithful representation of the in vivo airway while allowing for a controlled nutrient source and isolation from other tissues or immune cells. The methods used have significant differences based on tissue source, cell isolation, culture conditions, and assessment of culture purity. We modified and optimized a method for generating tracheal epithelial cultures from Syrian golden hamsters and characterized the cultures for cell composition and function. Soon after initial plating, the epithelial cells reached a high transepithelial resistance and formed tight junctions. The cells differentiated into a heterogeneous, multicellular culture containing ciliated, secretory, and basal cells after culture at an air-liquid interface (ALI). The, secretory cell populations initially consisted of MUC5AC-positive goblet cells and MUC5AC/CCSP double-positive cells, but the makeup changed to predominantly Clara cell secretory protein (CCSP)-positive Clara cells after 14 d. The ciliated cell populations differentiated rapidly after ALI as judged by the appearance of β tubulin IV-positive cells. The cultures produced mucus, CCSP, and trypsin-like proteases and were capable of wound repair as judged by increased expression of matrilysin. Our method provides an efficient, high-yield protocol for producing differentiated hamster tracheal epithelial cells that can be used for a variety of in vitro studies including tracheal cell differentiation, airway disease mechanisms, and pathogen-host interactions.


title: Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

text: Abstract Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12–798) and one on S2 subunit (aa 797–1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310–535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV.


title: Recombinant scFv Antibodies against E Protein and N Protein of Severe Acute Respiratory Syndrome Virus

text: Three single chain antibodies (scFv) against the proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) were isolated by phage display from an scFv antibody library. Bio-panning was carried out against immobilized purified envelope (E) and nucleocapsid (N) proteins of SARS-CoV. Their binding activity and specificity to E or N protein of SARS-CoV were characterized by phage-ELISA. Two of them, B10 and C20, could recognize non-overlapping epitopes of the E protein according to the two-site binding test result. Clone A17 could recognize N protein. The sequence of the epitope or overlapping epitope of scFv antibody A17 was PTDSTDNNQNGGRNGARPKQRRPQ. The affinity (equilibrium dissociation constant, K(d)) of SARS-CoV E protein was 5.7×10(−8) M for B10 and 8.9×10(−8) M for C20. The affinity of A17 for N protein was 2.1×10(−6) M. All three scFv antibodies were purified with affinity chromatography and determined by Western blot.


title: COVID-19 pandemic and its recovery time of patients in India: A pilot study

text: BACKGROUND AND AIMS: Covid-19 virus started from Wuhan, China and has brought the world down to its knees. It has catapulted as a venomous global phenomenon. This study focuses on the Covid-19 situation in India and its recovery time. METHOD: The study period is from March 1, 2020 to April 25, 2020. A random sample of 221 individuals found positive with Covid-19 from March 1, 2020 to 31st March is included in the study which is followed up April 25, 2020. There is a male preponderance in the sample with 66% of the Covid-19 patients being male and about 34% being female. Kaplan-Meier Product limit estimator, Kaplan-Meier survival curve and Log-rank test are used to analyze the recovery time of Covid-19 patients. RESULT: From the results of the study, it is found that the average recovery time of Covid-19 patients in India is 25 days (95% C.I. 16 days to 34 days). Only 4% of the patients get cured after 10 days of treatment. The recovery time of male and female patients is not statistically different. Recovery time of patients belonging to different age groups is also not statistically significant. CONCLUSION: This information on recovery time of Covid-19 patients will help planners to chalk out effective strategies.


title: Cost-Benefit of Stockpiling Drugs for Influenza Pandemic

text: We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.


title: Causes of Emergency Department Overcrowding and Blockage of Access to Critical Services in Beijing: A 2-Year Study

text: Abstract Background Emergency department (ED) overcrowding is a serious issue worldwide. Objectives This study was done to evaluate the degree of overcrowding in local “teaching hospitals” in Beijing, and to ascertain the apparent root causes for the pervasive degree of overcrowding in these EDs. Methods This is a multicenter cross-sectional study. The studied population included all ED patients from 18 metropolitan teaching hospital EDs in Beijing for calendar years 2013 and 2014. Patient characteristics, and the primary reasons that these patients sought care in these EDs, are described. Results The total numbers of annual emergency visits were 1,554,387 and 1,615,571 in 2013 and 2014, respectively. High acuity cases accounted for 4.6% and 5.5% of the total annual emergency visits in 2013 and 2014, respectively. The percentage of patients placed into “Observation” beds, which were created to accommodate patients deemed to have problems too complex to be treated in an inpatient bed, or to accommodate patients simply needing chronic care, was 11.9% and 13.1% in 2013 and 2014, respectively. The ED-boarded patients accounted for 2.71% and 2.6% of the total annual emergency visits in 2013 and 2014, respectively. The average waiting time to admit the ED-boarded patients was 37.1 h and 36.2 h in 2013 and 2014, respectively. Respiratory symptoms were the most common presenting complaints, and an upper respiratory infection was the most common ED diagnosis. Patients who had pneumonia or various manifestations of end-stage diseases, such as advanced dementia or multiple organ dysfunction, were the most common characteristics of patients who had stays in “Observation” units. Conclusions One principal reason for ED crowding in Beijing lies in the large numbers of patients who persist in the expectation of receiving ongoing care in the ED for minor illnesses. However, as is true in many nations, one of the other most important root causes of ED crowding is “access block,” the inability to promptly move patients deemed by emergency physicians to need inpatient care to an inpatient bed for that care. However, in our system, another challenge, not widely described as a contributor to crowding in other nations, is that doctors assigned to inpatient services have been empowered to refuse to admit patients perceived to have overly “complex” needs. Further, patients with multisystem illnesses or end-stage status, who need ongoing chronic care to manage activities of daily living, have begun to populate Beijing EDs in increasing numbers. This is an issue with various root causes.


ASI’s Consensus Guidelines: ABCs of What to Do and What Not During the COVID-19 Pandemic


title: Population-Based Incidence of Human Metapneumovirus in Hospitalized Children

text: BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established. METHODS: We conducted population-based prospective surveillance for HMPV in two U.S. counties among children <5 years hospitalized with ARI or fever for two years. Nasal/throat swabs were tested for HMPV by real-time RT-PCR and genotyped. RESULTS: Forty-two of 1104 (3.8%) children tested positive for HMPV. The overall annual rate of HMPV-associated hospitalizations per 1000 children <5 years was 1.2 (95%CI 0.9–1.6). This rate was highest in infants 0–5 months (4.9/1000 [95%CI 2.9–7.2]), followed by children 6–11 months (2.9/1000 [95%CI 1.4–4.7]). The annual rate of HMPV-associated hospitalizations was less than respiratory syncytial virus, but similar to influenza and parainfluenzavirus (PIV) 3 in all age groups. The mean age of children hospitalized with HMPV was 6 months. Bronchiolitis, pneumonia and asthma were the most common diagnoses in children with HMPV. All four HMPV subgroups were detected during both years at both sites. HPMV was most prominent from March through May. CONCLUSIONS: HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza and PIV3.


title: A prospective study of wheezing in young children: The independent effects of cockroach exposure, breast‐feeding and allergic sensitization

text: The objective of this study was to evaluate risk factors for persistent wheezing in a group of 2–4‐year‐old children after an index‐wheezing episode in infancy. Eighty infants who had been seen at the Emergency Department for an episode of acute wheezing were followed for 2 yr in this prospective study. Caregivers completed a questionnaire, and children underwent clinical evaluation and skin prick testing 2 yr following the index‐wheezing episode. Detection of respiratory viruses and analysis of exposure to major indoor allergens were carried out at enrollment. Immunoglobin E antibodies were measured at the beginning of the study and at the end of follow‐up, using the CAP system. Logistic regression analysis was performed to identify factors associated with persistent wheezing. Seventy‐three children (44 boys) completed the study. After 2 yr, 38 (52%) reported three or more wheezing episodes in the past 12 months (persistent wheezers). Independent risk factors for persistence of wheezing were allergic sensitization and exposure to cockroach allergen in the kitchen. Breast‐feeding for at least 1 month was a protective factor. A strong association between allergic sensitization and persistence of wheezing was found in a group of very young children living in a subtropical area.


title: Comparison of the Characteristics and Outcomes of Coronavirus Disease 2019 in Different Types of Family Infections in Taiwan

text: Background: There were some family infections of coronavirus disease 2019 (COVID-19) in Taiwan to date. This study aimed to investigate the clinical characteristics and outcomes of different types of family infections with COVID-19 and to share Taiwan’s experience. Material and methods: We collected cases of family infections of COVID-19 from 21 January 2020 to 16 March 2020. The data were collected from a series of press conference contents by Taiwan’s Central Epidemic Command Center (CECC). Results: During this period, there were six family infections in Taiwan, including two couple infections, one imported family cluster infection, and three domestic family cluster infections. Compared to the former two, the starters (cases 19, 24, and 27) of domestic family cluster infections showed longer symptom-onset to diagnosis (p = 0.02); longer symptom-onset to quarantine or isolation (p = 0.01); higher first-generation reproduction number (p = 0.03); and more critical presentation (endotracheal tube insertion and intensive care unit (ICU) care) (p < 0.01). In addition, compared to the former two, the starters of the latter were older, had no history of travel, and had more underlying diseases and more mortality. There are more contacts of domestic family cluster infections, making epidemiological investigations more difficult and expensive. However, the second-generation reproduction number of the above three families was zero. Conclusion: Domestic family cluster infections of COVID-19 have different characteristics and outcomes from couple infection and imported family cluster infections in this study.


title: Crystallization and preliminary crystallographic study of human coronavirus NL63 main protease in complex with an inhibitor

text: Human coronavirus NL63 mainly infects younger children and causes cough, fever, rhinorrhoea, bronchiolitis and croup. It encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of human coronavirus NL63 was crystallized in complex with a Michael acceptor. The complex crystals diffracted to 2.85 Å resolution and belonged to space group P4(1)2(1)2, with unit-cell parameters a = b = 87.2, c = 212.1 Å. Two molecules were identified per asymmetric unit.


title: Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles

text: Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. We describe here a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly and involves release of malfunctioning membrane-associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad-spectrum antiviral interferon-stimulated gene. Through analysis of the viperin-interactome, we identified the Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) as the cellular protein targeted by viperin. Viperin-induced antiviral activity, as well as C-particle release, was stimulated by GBF1 inhibition and knockdown and reduced by elevated levels of GBF1. Our results suggest that viperin targets flavivirus virulence by inducing the secretion of unproductive noninfectious virus particles via a GBF1-dependent mechanism. This as-yet-undescribed antiviral mechanism allows potential therapeutic intervention. IMPORTANCE The interferon response can target viral infection on almost every level; however, very little is known about the interference of flavivirus assembly. We show here that interferon, through the action of viperin, can disturb the assembly of tick-borne encephalitis virus. The viperin protein is highly induced after viral infection and exhibit broad-spectrum antiviral activity. However, the mechanism of action is still elusive and appears to vary between the different viruses, indicating that cellular targets utilized by several viruses might be involved. In this study, we show that viperin induces capsid particle release by interacting and inhibiting the function of the cellular protein Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1). GBF1 is a key protein in the cellular secretory pathway and is essential in the life cycle of many viruses, also targeted by viperin, implicating GBF1 as a novel putative drug target.


docid: eszfvtwa

title: Cutaneous autoimmune diseases during COVID 19 pandemic

text: The pandemic of infection with the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) causing the atypical pneumonia coronavirus disease 19 (Covid‐2019) has become a global health emergency. In parallel with the spread of the infection, there are new information on cutaneous involvement reminiscent to autoimmune diseases and concerns about the risk of disease and management of patients with cutaneous autoimmunity under immunosuppression.


title: Rotavirus strains in neglected animal species including lambs, goats and camelids

text: Surveillance of rotavirus infections and circulating strains in small ruminants (i.e. lambs, goats and camelids) has been a neglected research area in the past. However, recent years that have seen an intensification of surveillance in humans and livestock animals, where vaccines to reduce disease burden caused by Rotavirus A (RVA) are available, led to the efforts to better understand the epidemiology, ecology and evolution of RVA strains in other hosts, including lambs, goats and camelids. The aim of this review is to provide an update of the epidemiology and strain diversity of RV strains in these species through searching for relevant information in public data bases.


title: Bromoviruses (Bromoviridae)

text: The members of the family Bromoviridae have spherical or bacilliform virions with tri-segmented, single-stranded genomic RNAs, packaged in separate particles. Six genera including Alfamovirus, Anulavirus, Bromovirus, Cucumovirus, Ilarvirus, and Oleavirus are part of the family. RNA1 and RNA2 code for the replicase whereas RNA3 codes for movement and coat proteins. Genomic RNAs are infectious, but some species also require CP for infectivity. Members can encapsidate/accumulate sub-genomic RNAs, and/or defective or satellite RNAs. RNA replication occurs inside membranous spherules, and the role of host factors in RNA replication have been documented. Frequent RNA-RNA recombination and segment reassortment processes were observed among bromovirids. Transmission occurs mechanically, via pollen, seeds or insects. Host range varies from narrow to wide, infecting herbaceous plants, shrubs and trees, with some members causing major epidemics.


docid: yxskgmqg

title: An unilateral purpuric rash in a patient with COVID‐19 infection


title: Neurological Consequences of 2019-nCoV Infection: A Comprehensive Literature Review

text: First identified in November 2019 in Hubei Province, the coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 soon spread worldwide to become a global health pandemic. The COVID-19 preferentially damages the respiratory system that produces symptoms such as fever, cough, and shortness of breath. However, the infection often tends to disseminate to involve various organ systems. Recent evidence indicates that SARS-CoV-2 can cause significant neurological damage and resultant neurological symptoms and complications. Here, we provide a comprehensive and thorough review of original articles, case reports, and case series to delineate the possible mechanisms of nervous system invasion and damage by SARS-CoV-2 and subsequent consequences. We divided the neurological manifestations into three categories: (1) Central Nervous System involvement, (2) Peripheral Nervous System manifestations, and (3) Skeletal Muscle Injury. Headache and dizziness were found to be the most prevalent symptoms followed by impaired consciousness. Among the symptoms indicating peripheral nervous system invasion, anosmia and dysgeusia were commonly reported. Skeletal muscle injury predominantly presents as myalgia. In addition, encephalitis, myelitis, cerebrovascular disease, Guillain-Barre syndrome, and Miller Fischer syndrome were among the commonly noted complications. We also emphasized the association of pre-existing comorbidities with neurological manifestations. The aim of this review is to provide a deeper understanding of the potential neurological implications to help neurologists have a high index of clinical suspicion allowing them to manage the patient appropriately.


title: The role of climate during the COVID‐19 epidemic in New South Wales, Australia

text: Previous research has identified a relationship between climate and occurrence of SARS‐CoV and MERS‐CoV cases, information that can be used to reduce the risk of infection. Using COVID‐19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time series analysis to investigate the relationship between 749 cases of locally acquired COVID‐19 and daily rainfall, 9 a.m. and 3 p.m. temperature, and 9 a.m. and 3 p.m. relative humidity. Lower 9 a.m. relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID‐19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID‐19 cases.


title: Comparison of the 5′ and 3′ termini of tomato ringspot virus RNA1 and RNA2: Evidence for RNA recombination

text: Abstract The sequences of the 5′ terminal 1140 and 3′ terminal 1546 nt of tomato ringspot virus (TomRSV) RNA1 have been determined. These sequences share a high degree of nucleotide sequence similarity with the previously determined TomRSV RNA2 sequence. Eighty-eight percent of the 5' terminal 907 nt of TomRSV RNA1 and RNA2 contain identical nucleotide residues; the first 459 nt are identical at all positions, whereas the next 447 nt are identical at only 75.8% of the nucleotide positions. The region of similarity includes not only the 5' nontranslated leader but also sequence probably encoding polyproteins. The 3′ terminal 1533 nt of TomRSV RNA1 and RNA2 are identical and are noncoding. The sequences common to RNA1 and RNA2 account for almost 35% of the total genomic sequence. It is possible that the similar sequences at both ends of TomRSV RNA1 and RNA2 are a result of recombination between these two genomic RNA components.


title: Influenza vaccination coverage rates in Europe – covering five consecutive seasons (2001–2006) in five countries

text: Objective To understand potential drivers and barriers to influenza vaccination in the general population. Methods 47 982 household surveys were conducted in five European countries between 2001 and 2006. Results Overall influenza vaccination coverage increased over the years and reached 26·2% in 2005/06. Among the elderly ≥65 years, the rate increased significantly to 67·8% (2005/06). The most common reason for being vaccinated over the 5 years was the perception of influenza as a serious illness, which people want to avoid. The main reason for not getting vaccinated among those never previously vaccinated was feeling that they were unlikely to catch influenza. A recommendation by the family physician was the most encouraging factor for vaccination.


title: Virus Classification by Pairwise Sequence Comparison (PASC)

text: Pairwise sequence comparison (PASC) is a molecular classification tool for viruses. It calculates the pairwise identities of virus sequences within a virus family and displays their distributions, and can help determine demarcations at different taxonomic levels such as strain, species, genus, and subfamily levels. PASC has many advantages over conventional virus classification methods. The tool has been successfully applied to several virus families, although it may not work well for virus families with highly diverse genome organization. The PASC tool at NCBI established distributions of identity for a number of virus families. A new virus sequence can be tested with this system within a few minutes to suggest the taxonomic position of the virus in a specific family. This system eliminates potential discrepancies in the results caused by different algorithms and/or different data used by the virology community. Data in the system can be updated automatically to reflect changes in virus taxonomy and additions of new virus sequences to the public database. The web interface of the tool makes it easy to navigate and perform analyses.


title: Evaluation of real-time reverse-transcription loop-mediated isothermal amplification assay for clinical diagnosis of West Nile virus in patients

text: BACKGROUND & OBJECTIVES: West Nile virus (WNV) is a mosquito-borne flavivirus. The disease can be diagnosed by isolation followed by fluorescent antibody tests, enzyme-linked immunosorbent assay and polymerase chain reaction (PCR) assay. These diagnostic methods are laborious and time-consuming. The present study was aimed to evaluate the real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, early and accurate diagnosis of WNV. METHODS: A one-step single tube accelerated quantitative RT-LAMP assay was evaluated by targeting the Env gene of WNV. The gene amplification was accomplished by incubating the reaction mixture at 63°C for 60 min in both real time turbidimeter as well as routine laboratory water bath/dry heating bath. To rule out contamination issues, proper negative controls, including no template, no primer; and no enzyme, were always kept alongside each run. The RT-LAMP assay was evaluated on 105 clinical samples from individuals having ocular infection. RESULTS: Of the 105 samples tested, 27 were positive for WNV by RT-LAMP assay. The comparative evaluation with conventional RT-PCR revealed 100 per cent accordance with sensitivity and specificity of 100 and 95 per cent, respectively. The specificity of this assay was confirmed with serum samples obtained from patients with dengue and chikungunya. INTERPRETATION & CONCLUSIONS: The RT-LAMP test seemed to be a sensitive and specific method for rapid detection of WNV infection and would be useful for rapid screening of a large number of clinical samples in endemic areas during outbreaks.


title: Different evolutionary trajectories of vaccine-controlled and non-controlled avian infectious bronchitis viruses in commercial poultry

text: To determine the genetic and epidemiological relationship of infectious bronchitis virus (IBV) isolates from commercial poultry to attenuated live IBV vaccines we conducted a phylogenetic network analysis on the full-length S1 sequence for Arkansas (Ark), Massachusetts (Mass) and Delmarva/1639 (DMV/1639) type viruses isolated in 2015 from clinical cases by 3 different diagnostic laboratories. Phylogenetic network analysis of Ark isolates showed two predominant groups linked by 2 mutations, consistent with subpopulations found in commercial vaccines for this IBV type. In addition, a number of satellite groups surrounding the two predominant populations were observed for the Ark type virus, which is likely due to mutations associated with the nature of this vaccine to persist in flocks. The phylogenetic network analysis of Mass-type viruses shows two groupings corresponding to different manufacturers vaccine sequences. No satellite groups were observed for Mass-type viruses, which is consistent with no persistence of this vaccine type in the field. At the time of collection, no vaccine was being used for the DMV/1639 type viruses and phylogenetic network analysis showed a dispersed network suggesting no clear change in genetic distribution. Selection pressure analysis showed that the DMV/1639 and Mass-type strains were evolving under negative selection, whereas the Ark type viruses had evolved under positive selection. This data supports the hypothesis that live attenuated vaccine usage does play a role in the genetic profile of similar IB viruses in the field and phylogenetic network analysis can be used to identify vaccine and vaccine origin isolates, which is important for our understanding of the role live vaccines play in the evolutionary trajectory of those viruses.


title: COVID-19 pandemic reveals the peril of ignoring metadata standards

text: Efficient response to the pandemic through the mobilization of the larger scientific community is challenged by the limited reusability of the available primary genomic data. Here, the Genomic Standards Consortium board highlights the essential need for contextual genomic data FAIRness, for empowering key data-driven biological questions.


title: Resilience in the time of pandemic: The experience of community pharmacists in Ontario during COVID-19

text: BACKGROUND: As a result of the COVID-19 pandemic, there has been a significant disruption of the practice of pharmacy. Importantly, in many parts of the world, this disruption occurred literally overnight, requiring pharmacists to demonstrate significant adaptability and resiliency in order to manage continuing and in some cases expanding needs of patients. OBJECTIVES: The objective of this research was to characterize how community pharmacy in Ontario (Canada) responded to the COVID-19 pandemic of winter/spring 2020, in particula in understanding what factors may influence or predict resiliency of individual practitioners and their workplaces. METHODS: One-on-one interviews mediated through technology (Microsoft Teams) were used, following a semi-structured interview protocol. Verbatim transcripts were produced and analyzed by two independent researchers, using an inductive coding process to identify and characterize themes. RESULTS: A total of 21 pharmacists participated in this study. Six themes were identified: a) use of and comfort with technology; b) early adoption of corporate and professional guidance; c) workplaces that emphasized task-focus rather than multi-tasking were more resilient; d) scheduling methods and practices in the workplace are important for personal resilience; e) dedicated specialty staff allowed pharmacists to focus on their work; and f) provision of personal protective equipment was essential. CONCLUSIONS: Traditionally, resilience in professional practice has been characterized as a personal, not a workplace, issue. This study suggests that personal resiliency for pharmacists requires substantial workplace support; further work in this area is required to better understand how pharmacists adapt to complex and difficult situations such as pandemics.


title: Why Kill the Cabin Boy?

text: The task of combatting and defeating Covid-19 calls for drastic measures as well as cool heads. It also requires that we keep our nerve and our moral integrity. In the fight for survival, as individuals and as societies, we must not lose our grip on the values and the compassion that make individual and collective survival worth fighting for, or indeed worth having.(1)


title: Chapter 8 Suidae and Tayassuidae

text: Abstract The Suidae and Tayassuidae live on all continents except Antarctica. True wild boars were indigenous to Europe and Asia and are the ancestors to the domestic pig; with whom they share the same scientific name Sus scrofa. Wild boars have been introduced to the Americas and many islands. Because of the close genetic relationship, in many areas they have interbred with domestic pigs and formed considerable populations of feral suids that represent wild boar and feral pig crosses. Wild suid populations are relatively hardy and most disease research has been focused on their potential as a reservoir for diseases of concern for commercial pig production. The Togian Island babirusa, pygmy hog, Visayan warty pig, Javan warty pig, and Chacoan peccary are endangered. For all species, hunting, habitat loss, and hybridization are important threats to conservation.


Convalescent plasma therapy in the treatment of COVID-19: practical considerations: Correspondence


title: Investigation of a large waterborne acute gastroenteritis outbreak caused by group B rotavirus in Maharashtra state, India

text: An acute gastroenteritis outbreak at Devli Karad village, Maharashtra, India with an attack rate of 22.6% affected mainly adolescent and adult population. The viral investigations conducted on fecal specimens of patients hospitalized indicated the presence of rotavirus B (RVB) using RNA polyacrylamide gel electrophoresis and reverse transcription polymerase chain reaction. The samples collected from the source of drinking water also showed the presence of the only RVB. Absence of other viral agents and identification of RVB of genotype G2 as the etiological agent of the acute gastroenteritis outbreak highlights, the necessity of monitoring RVB, the viral agent known for its large outbreak potential.


title: Data and preprints

text: Journal requirements for data deposition and encouragement of deposition of preprints in a community preprint server are stated policy. Because many authors put data in a public repository only upon publication and many still ask about the status of preprints, here is a further statement of our position.


title: Delays in Stroke Onset to Hospital Arrival Time During COVID-19

text: BACKGROUND AND PURPOSE: The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services. We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong. METHODS: We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020–March 24, 2020). We compared the stroke onset to hospital arrival (onset-to-door) time and timings of inpatient stroke pathways with patients admitted during the same period in 2019 (pre–COVID-19: January 23, 2019–March 24, 2019). RESULTS: Seventy-three patients in COVID-19 were compared with 89 patients in pre–COVID-19. There were no significant differences in age, sex, vascular risk factors, nor stroke severity between the 2 groups (P>0.05). The median stroke onset-to-door time was ≈1-hour longer in COVID-19 compared with pre–COVID-19 (154 versus 95 minutes, P=0.12), and the proportion of individuals with onset-to-door time within 4.5 hours was significantly lower (55% versus 72%, P=0.024). Significantly fewer cases of transient ischemic attack presented to the hospital during COVID-19 (4% versus 16%, P=0.016), despite no increase in referrals to the transient ischemic attack clinic. Inpatient stroke pathways and treatment time metrics nevertheless did not differ between the 2 groups (P>0.05 for all comparisons). CONCLUSIONS: During the early containment phase of COVID-19, we noted a prolongation in stroke onset to hospital arrival time and a significant reduction in individuals arriving at the hospital within 4.5 hours and presenting with transient ischemic attack. Public education about stroke should continue to be reinforced during the COVID-19 pandemic.


title: Synthetic biology for bioengineering virus‐like particle vaccines

text: Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus‐like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. Several VLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target‐specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described. When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry.


title: The new (dis)order in RNA regulation

text: RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.


The challenges of establishing adequate capacity for SARS‐CoV‐2 testing


title: Peptides Corresponding to the Predicted Heptad Repeat 2 Domain of the Feline Coronavirus Spike Protein Are Potent Inhibitors of Viral Infection

text: BACKGROUND: Feline infectious peritonitis (FIP) is a lethal immune-mediated disease caused by feline coronavirus (FCoV). Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2) sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5) at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5) exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α), and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.


title: Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis

text: Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.


title: Evaluation of Passive Immunity Induced by Immunisation Using Two Inactivated gE-deleted Marker Vaccines against Infectious Bovine Rhinotracheitis (IBR) in Calves

text: Different types of vaccines against Infectious Bovine Rhinotracheitis (IBR) are commercially available. Among these, inactivated glycoprotein E (gE)-deleted marker vaccines are commonly used, but their ability to induce passive immunity is poorly known. Here, we evaluated the passive immunity transferred from dams immunised with commercial inactivated gE-deleted marker vaccines to calves. We vaccinated 12 pregnant cattle devoid of neutralising antibodies against Bovine alphaherpesvirus 1 (BoHV-1) and divided them into two groups with 6 animals each. Both groups were injected with a different inactivated gE-deleted marker vaccine administrated via intranasal or intramuscular routes. An additional 6 pregnant cattle served as the unvaccinated control group. After calving, the number of animals in each group was increased by the newborn calves. In the dams, the humoral immune response was evaluated before calving and, subsequently, at different times until post-calving day 180 (PCD180). In addition, the antibodies in colostrum, milk, and in serum samples from newborn calves were evaluated at different times until PCD180. The results indicated that inactivated glycoprotein E (gE)-deleted marker vaccines are safe and produce a good humoral immune response in pregnant cattle until calving and PCD180. Moreover, results showed that, in calf serum, passive immunity persists until PCD180.


title: SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood from the San Francisco Bay Area

text: We report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.


title: Model of health? Distributed preparedness and multi-agency interventions surrounding UK regional airports

text: Abstract The liberalisation of the European aviation sector has multiplied paths of entry into the United Kingdom (UK) for the international traveller. These changing mobilities necessitate a reconceptualisation of the border as a series of potentially vulnerable nodes occurring within, and extending beyond, national boundaries. In this paper, we consider the border through the lens of port health, the collective term for various sanitary operations enacted at international transport terminals. In the UK, a critical player in the oversight of port health is the Health Protection Agency (HPA), which became a non-Departmental public body in 2005. A major part of port health is preparedness, a set of techniques aimed at managing, and responding to, emergencies of public health concern. More recently, certain jurisdictions have embarked on public health preparedness work across a number of different geographical scales. Using methods pioneered by the military, this form of ‘distributed preparedness’ is of increased interest to social science and medical scholars. With reference to case studies conducted in localities surrounding two UK regional airports following the 2009–10 H1N1 influenza pandemic, we consider the extent to which distributed preparedness as a concept and a set of practices can inform current debates - in the UK, and beyond - concerning interventions at the border ‘within’.


title: Vaccine prevention of acute otitis media

text: The incidence of acute otitis media (AOM) in infants and young children has increased dramatically in recent years in the United States. AOM often follows upper respiratory tract infections due to pathogens such as respiratory syncytial virus (RSV), influenza virus, and parainfluenza virus (PIV). These viruses cause eustachian tube dysfunction that is critical to the pathogenesis of AOM. Vaccines against these viruses would likely reduce the incidence of AOM. In three previous studies, influenza virus vaccines reduced the incidence of AOM by 30% to 36%. Vaccines to prevent infections with RSV and PIV type 3 are undergoing clinical testing at this time. Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the three most common AOM pathogens. Heptavalent pneumococcal conjugate vaccine is effective in preventing invasive disease and AOM caused by serotypes contained in the vaccine. Vaccine candidates for NTHi and M. catarrhalis are under development.


title: Donor-derived infection—the challenge for transplant safety

text: Organ transplantation, including of the heart, lung, kidney, liver, pancreas, and small bowel, is considered the therapy of choice for end-stage organ failure. Each year, over 70,000 organs are implanted worldwide. One donor may provide multiple organs, as well as corneas and other tissues, for multiple recipients. The degree of risk for transmission of infection carried with grafts, notably of viruses, is largely unknown and, for a specific organ, difficult to assess. The approach to microbiological screening of organ donors varies with national and regional regulations and with the availability and performance of microbiological assays used for potential donors. Transmission of both expected or common, and unexpected infections has been observed in organ transplants, generally recognized after development of clusters of infections among recipients of organs from a common donor. Other than for unusual or catastrophic events, few data exist that define the incidence and manifestations of donor-derived infections or the ideal assays to use in screening to prevent such transmissions. Absolute prevention of the transmission of donor-derived infections in organ transplantation is not possible. However, improvements in screening technologies will enhance the safety of transplantation in the future. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrneph.2014.159) contains supplementary material, which is available to authorized users.


COVID-19: before stopping specific infection control measures, be sure to exclude the diagnosis


title: Fatal canine distemper virus infection of giant pandas in China

text: We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.


title: Advancing E-Mental Health in Canada: Report From a Multistakeholder Meeting

text: The need for e-mental health (electronic mental health) services in Canada is significant. The current mental health care delivery models primarily require people to access services in person with a health professional. Given the large number of people requiring mental health care in Canada, this model of care delivery is not sufficient in its current form. E-mental health technologies may offer an important solution to the problem. This topic was discussed in greater depth at the 9th Annual Canadian E-Mental Health Conference held in Toronto, Canada. Themes that emerged from the discussions at the conference include (1) the importance of trust, transparency, human centeredness, and compassion in the development and delivery of digital mental health technologies; (2) an emphasis on equity, diversity, inclusion, and access when implementing e-mental health services; (3) the need to ensure that the mental health workforce is able to engage in a digital way of working; and (4) co-production of e-mental health services among a diverse stakeholder group becoming the standard way of working.


Gastroenterologists and Patients Report High Satisfaction Rates with Telehealth Services during the Novel Coronavirus 2019 (COVID-19) Pandemic


title: A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam

text: Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs) play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs) including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders’ reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.


Comment on “Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus”


title: In vitro assembled, recombinant infectious bronchitis viruses demonstrate that the 5a open reading frame is not essential for replication

text: Abstract Molecular clones of infectious bronchitis virus (IBV), derived from the Vero cell adapted Beaudette strain, were constructed, using an in vitro assembly method. In vitro transcribed RNA from a cDNA template that had been constructed from seven cDNA fragments, encompassing the entire genome of IBV, was electroporated into BHK-21 cells. The cells were overlaid onto the susceptible Vero cells and viable virus was recovered from the molecular clone. The molecularly cloned IBV (MIBV) demonstrated growth kinetics, and plaque size and morphology that resembled the parental Beaudette strain IBV. The recombinant virus was further manipulated to express enhanced green fluorescent protein (EGFP) by replacing an open reading frame (ORF) of the group-specific gene, ORF 5a, with the EGFP ORF. The rescued recombinant virus, expressing EGFP (GIBV), replicated to lower viral titers and formed smaller plaques compared to the parental virus and the MIBV. After six passages of GIBV, a minority of plaques were observed that had reverted to the larger plaque size and virus from these plaques no longer expressed EGFP. Direct sequencing of RT-PCR products derived from cells infected with the plaque-purified virus, which had lost expression of EGFP, confirmed loss of the EGFP ORF. The loss of EGFP expression (Δ5a IBV) was also accompanied by reversion to growth kinetics resembling the standard virus and intact recombinant virus. This study demonstrates that the 5a ORF is not essential for viral multiplication in Vero cells.


title: Emergency room neurology in times of COVID‐19: malignant ischaemic stroke and SARS‐CoV‐2 infection

text: We report the case of a 36-year-old health care worker who suffered a subacute infarct with a mild deviation of the midline, and a large vessel occlusion with a free-floating thrombus in the ascending aorta in the context of a SARS-CoV-2 infection. With this case we want to increase the awareness about severe forms of systemic ischemia and stroke in patients with signs of COVID infection.


title: Computational insights into tetracyclines as inhibitors against SARS-CoV-2 M(pro) via combinatorial molecular simulation calculations

text: The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (M(pro)). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 M(pro) crystal structure. Molecular docking simulation predicted the docking score >−7 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 M(pro). The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 M(pro) which can used in combinational therapy against SARS-CoV-2 infection.


title: Malnutrition and gastroenteritis in The Gambia

text: Abstract There is a strong association between failure to thrive and diarrhoeal disease in young Gambian children. The high prevalence of diarrhoeal disease seen is not due to frequent attacks of “acute infantile diarrhoea” of viral origin. The picture of protracted diarrhoea is almost certainly due to colonization of the upper bowel and the high prevalence demonstrated to be at least partly due to the environment to which the children are exposed, particularly in terms of food and water hygiene. Until this cycle of upper bowel colonization and protracted diarrhoea is broken, a diet-based nutrition programme cannot be expected to function effectively.


title: Analysis of Risk Perceptions and Related Factors Concerning COVID-19 Epidemic in Chongqing, China

text: OBJECTIVE: To assess perceptions of risk and related factors concerning COVID-19 epidemic among residents in Chongqing city, China. METHODS: With convenience sampling, a web questionnaire survey was conducted among 476 residents living in Chongqing on February 13rd to 14th in 2020, when citizens just started to get back to work. RESULTS: Residents’ estimated perceived risks were (4.63 ± 0.57), (4.19 ± 0.76), (3.23 ± 0.91) and (2.29 ± 0.96) for the infectivity, pathogenicity, lethality and self-rated infection possibility of COVID-19, respectively. Females (OR = 4.234), people with income ≥ 2000 yuan (2000–4999 yuan: OR = 5.052, 5000–9999 yuan: OR = 4.301, ≥ 10,000 yuan: OR = 23.459), the married status (OR = 1.811), the divorced status, widows or widowers (OR = 3.038), people living with families including children (OR = 5.085) or chronic patients (OR = 2.423) had a higher perceived risk level, as well as people who used free media websites (OR = 1.756), community workers (OR = 4.064) or community information platforms (OR = 2.235) as main media information sources. The perceived risk increased by 4.9% for every one-year increase of age. People who used WeChat contacts (OR = 0.196) as the main media information source, reported a lower perceived risk. CONCLUSION: Residents reported a high level of risk perception towards COVID-19 in Chongqing and it was impacted by the population demographic characteristics. Media information sources, including community information platforms and community workers may cause the increase of public risk perceptions.


title: Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase

text: All positive-stranded RNA viruses with genomes >∼7 kb encode helicases, which generally are poorly characterized. The core of the nidovirus superfamily 1 helicase (HEL1) is associated with a unique N-terminal zinc-binding domain (ZBD) that was previously implicated in helicase regulation, genome replication and subgenomic mRNA synthesis. The high-resolution structure of the arterivirus helicase (nsp10), alone and in complex with a polynucleotide substrate, now provides first insights into the structural basis for nidovirus helicase function. A previously uncharacterized domain 1B connects HEL1 domains 1A and 2A to a long linker of ZBD, which further consists of a novel RING-like module and treble-clef zinc finger, together coordinating three Zn atoms. On substrate binding, major conformational changes were evident outside the HEL1 domains, notably in domain 1B. Structural characterization, mutagenesis and biochemistry revealed that helicase activity depends on the extensive relay of interactions between the ZBD and HEL1 domains. The arterivirus helicase structurally resembles the cellular Upf1 helicase, suggesting that nidoviruses may also use their helicases for post-transcriptional quality control of their large RNA genomes.


Competition law in times of crisis—tackling the COVID-19 challenge: Australian Competition and Consumer Commission


title: Selection of DNA aptamers against DC-SIGN protein

text: Dendritic cells (DCs) are professional antigen-presenting cells and have come to be appreciated as critical controllers of the immune response, especially T cell responses. Apart from presenting antigens to T cells, DCs carry out many other functions in regulating immunity. DC-specific intercellular adhesion molecule (ICAM)-3 grabbing non-integrin (DC-SIGN) is a novel receptor that plays an important role in DC migration and adhesion, the inflammatory response, T cell activation, initiating the immune response, and immune escape of pathogens and tumors. DC-SIGN mediates DC binding to ICAM-3 on the T cell surface and ICAM-2 on the endothelial cell (EC) surface, and takes part in the initial interaction between DC and T cells or vascular ECs. The procedure of systematic evolution of ligands by exponential enrichment (SELEX) is a method in which single-stranded oligonucleotides are selected from a wide variety of sequences, based on their interaction with a target molecule. In this study, we selected DNA aptamers against DC-SIGN protein by SELEX, and measured their binding affinity for DC-SIGN. Finally, an appropriate aptamer with high affinity for DC-SIGN was obtained, and it blocked DC adhesion to ECs as effectively as anti-DC-SIGN monoclonal antibody.


title: Preliminary crystallographic analysis of avian infectious bronchitis virus main protease

text: Infectious bronchitis virus (IBV) is the prototype of the genus Coronavirus. It causes a highly contagious disease which affects the respiratory, reproductive, neurological and renal systems of chickens, resulting great economic losses in the poultry industry worldwide. The coronavirus (CoV) main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, is an attractive target for antiviral drug design. In this study, IBV M(pro) was overexpressed in Escherichia coli. Crystals suitable for X-ray crystallography have been obtained using microseeding techniques and belong to space group P6(1)22. X-ray diffraction data were collected in-house to 2.7 Å resolution from a single crystal. The unit-cell parameters were a = b = 119.1, c = 270.7 Å, α = β = 90, γ = 120°. Three molecules were predicted to be present in the asymmetric unit from a calculated self-rotation function.


title: Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products

text: ABSTRACT: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements. GRAPHIC ABSTRACT: [Image: see text]


title: The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation

text: Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation.


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title: Surveillance operation for the 141st confirmed case of Middle East Respiratory Syndrome coronavirus in response to the patient’s prior travel to Jeju Island

text: The provincial government of Jeju, South Korea, was notified that a 42-year-old man infected with the Middle East Respiratory Syndrome (MERS) coronavirus had gone sightseeing in Jeju Island. Although the visiting period might be interpreted as the incubation period of MERS, the province decided to conduct active surveillance to prevent a worst-case scenario. Based on the channel of movement of the patient, healthy isolation and active monitoring were conducted for persons who came in contact with the patient. During the active surveillance, none of the 56 persons in self-isolation and 123 persons under active monitoring became infected. This fact supports that MERS is not contagious during the incubation period.


title: Genetic characterization of human bocavirus among children with severe acute respiratory infection in China

text: Summary Objectives To investigate the genetic character of Human bocavirus (HBoV) among children with severe acute respiratory infection (SARI) in China. Methods We screened 993 respiratory samples for HBoV by PCR among hospitalized children with SARI between September 2007 and March 2014. Four of HBoV1 samples were selected for complete genomes analysis by next-generation sequencing. Results The results show that 200 (20.1%) out of 993 samples were HBoV-positive, most of these HBoV belong to HBoV1 subtype (n = 197), HBoV2 (n = 1) and HBoV3 (n = 2) were also detected. Fifty (5.04%) of 993 SARI patient were detected as HBoV-positive only. Four HBoV1 genomes in this study were conserved and showed no significant difference among the nucleotide diversity from different regions. Analyses of evolutionary rates showed that NS1 exhibited the highest degree of conservation while the VP1 gene exhibited the fastest rate of evolution at 4.20 × 10−4 substitutions/site/year. The nucleotide deletions and substitutions occurred in NP1 and VP1 represented novel molecular signatures enabling subtype differentiation between HBoVs. Conclusions We described some new characteristics in the epidemiology of HBoV among children with SARI, these data will significantly expand the current knowledge of HBoV epidemic and genomic characterization among children with SARI.


title: The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach

text: The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.


title: Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”

text: A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC(50) value of about 0.6 μM. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-(3)H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC(50) value of 28.8 μM and 21.5 μM, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 μM.


title: Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model

text: Bacillus Calmette-Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid (IL2Rg−/−) (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b(+) F4/80(+) after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro-differential genes Spi-1 proto-oncogene, early growth response protein 1, nuclear factor (NF)-κB and proto-oncogene c-Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.


Return to sports after COVID-19 infection: Do we have to worry about myocarditis?