In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Q: The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates : bioRxiv preprint against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19. author/funder. All rights reserved. No reuse allowed without permission. : bioRxiv preprint known evidences reported in the literature, we also discussed several putative mechanisms of the anti-SARS-CoV-2 effects for CVL218 or other PARP1 inhibitors to be involved in the treatment of COVID-19. Overall, our results indicated that the PARP1 inhibitor CVL218 identified by our drug repositioning pipeline may serve as an effective therapeutic agent against COVID-19. Results The overview of our data-driven drug repositioning framework is shown in Figure 1A . We first constructed a virus related knowledge graph consisting of drug-target interactions, protein-protein interactions and similarity networks from publically available databases (Methods). Three different types of nodes (i.e., drugs, human targets and virus targets) within the knowledge graph were connected through edges describing their interactions, associations or similarities to establish bridges of information aggregation and knowledge mining. We then applied a network-based knowledge mining algorithm to predict an initial list of drug candidates that can be potentially used to treat SARS-CoV-2 infection ( Figure 1B and Methods). Next, we further narrowed down the list of drug candidates with the previously reported evidences of antiviral activities based on the text mining results from the large-scale literature texts, which were derived through a deep learning based relation extraction method named BERE [4] ( Figure 1C and Methods), followed by a minimum of manual checking. After that, we used the connectivity map analysis approach [5] with the gene expression profiles of ten SARS-CoV-infected patients [6] to further refine the list of drug candidates against SARS-CoV-2 ( Figure 1D , Table 1, Table S1 and Methods). The above screening process revealed that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor PJ-34 could potentially have the antiviral activities against SARS-CoV-2. 4 author/funder. All rights reserved. No reuse allowed without permission.

A: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
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Q: Background: Since 2010, outbreaks of genotype 2 (G2) porcine epidemic diarrhea virus (PEDV) have caused high mortality in neonatal piglets and have had devastating impacts on the swine industry in many countries. A reliable serological assay for evaluating the PEDV-specific humoral and mucosal immune response is important for disease survey, monitoring the efficacy of immunization, and designing strategies for the prevention and control of PED. Two PEDV spike (S) glycoprotein-based indirect enzyme-linked immunosorbent assays (ELISAs) were developed using G2b PEDV-Pintung 52 (PEDV-PT) trimeric full-length S and truncated S 1-501 proteins derived from the human embryonic kidney (HEK)-293 cell expression system. The truncated S 1-501 protein was selected from a superior expressed stable cell line. The sensitivity and specificity of these two ELISAs were compared to immunostaining of G2b PEDV-PT infected cells and to a commercial nucleocapsid (N)-based indirect ELISA kit using a panel of PEDV negative and hyperimmune sera. The commercial N-based ELISA exhibited a sensitivity of 37%, a specificity of 100%, and a fair agreement (kappa = 0.37) with the immunostaining result. In comparison, the full-length S-based ELISA showed a sensitivity of 97.8%, a specificity of 94%, and an almost perfect agreement (kappa = 0.90) with the immunostaining result. Interestingly, the S 1-501 -based ELISA had even higher sensitivity of 98.9% and specificity of 99.1%, and an almost perfect agreement (kappa = 0.97) with the immunostaining result. A fair agreement (kappa< 0.4) was seen between the commercial N-based ELISA and either of our S-based ELISAs. However, the results of the full-length S-based ELISA shared an almost perfect agreement (kappa = 0.92) with that of S 1-501 -based ELISA. (Continued on next page)

A: Development and comparison of enzyme- linked immunosorbent assays based on recombinant trimeric full-length and truncated spike proteins for detecting antibodies against porcine epidemic diarrhea virus
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Q: Background: The evaluation of children with purpuric rash and fever (PRF) is controversial. Although many of them have viral infections, on occasion such patients may be infected with Neisseria meningitidis. We described all children aged 0e18 years with PRF in southern Israel during the period 2005 2016 and compared their microbiologic, laboratory, clinical and outcome characteristics in relation to various etiologies of this syndrome. Methods: Data were summarized from electronic patient and microbiology files. Viral diagnoses were made by serology and/or PCR. Results: Sixty-nine children with PRF were admitted; 30 (43.48%), 9 (13.04%) and 30 (43.48%) had a syndrome of bacterial, viral or non-established etiology, respectively. N. meningitidis infection was diagnosed in 16/69 (23.19%) patients and in 16/30 (53.33%) patients with bacterial etiology; 14/30 (46.67%) patients suffered from a non-invasive bacterial disease (9 with Rickettsial disease). Adenovirus and Influenza B (3 and 2 cases, respectively) represented the most frequent etiologic agents among patients with viral etiology. More patients with PRF of bacterial etiology were older, of Bedouin ethnicity, looked ill on admission, had higher Pediatrics and Neonatology (2019) 60, 556e563 rates of meningitis and were treated more frequently with antibiotics compared with patients with non-bacterial PRF. Fatality rates among patients with bacterial, viral and non-established etiology were 5/30 (16.7%), 0% and 2/39 (5.1%). Conclusions: Although PFR was uncommon, high rates of meningococcal infections were recorded in children with PRF, which was associated with high fatality rates. Rickettsial infections were frequent, emphasizing the need for a high index of suspicion for this disease in endemic geographic areas.

A:
Original Article
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