cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.16616635.v2
title: Drug repositioning against COVID-19: a first line treatment

description: COVID-19 disease caused by the SARS-CoV-2 virus has shaken our health and wealth foundations. Although COVID-19 vaccines will become available allowing for attenuation of disease progression rates, distribution of vaccines can create other challenges and delays. Hence repurposed drugs against SARS-CoV-2 can be an attractive parallel strategy that can be integrated into routine clinical practice even in poorly-resourced countries. The present study was designed using knowledge of viral pathogenesis and pharmacodynamics of broad-spectrum antiviral agents (BSAAs). We carried out the virtual screening of BSAAs against the SARS-CoV-2 spike glycoprotein, RNA dependent RNA polymerase (RdRp), the main protease (Mpro) and the helicase enzyme of SARS-CoV-2. Imatinib (a tyrosine kinase inhibitor), Suramin (an anti-parasitic), Glycyrrhizin (an anti-inflammatory) and Bromocriptine (a dopamine agonist) showed higher binding affinity to multiple targets. Further through molecular dynamics simulation, critical conformational changes in the target protein molecules were revealed upon drug binding which illustrates the favorable binding conformations of antiviral drugs against SARS-CoV-2 target proteins. The resulting drugs from the present study in combination and in cocktails from the arsenal of existing drugs could reduce the translational distance and could offer substantial clinical benefit to decrease the burden of COVID-19 illness. This also creates a roadmap for subsequent viral diseases that emerge. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16635406
title: Identification of novel potential inhibitors of varicella-zoster virus thymidine kinase from ethnopharmacologic relevant plants through an <i>in-silico</i> approach

description: Although Varicella or chickenpox infection which is caused by the varicella-zoster virus (VZV) has significantly been managed through vaccination, it remains an infection that poses threats to the nearest future due to therapeutic drawbacks. The focus of this research was geared towards <i>in silico</i> screening for the identification of novel compounds in plants of ethnopharmacological relevance in the treatment of chicken pox in West Africa. The work evaluated 65 compounds reported to be present in <i>Achillea millefolium, Psidium guajava</i> and <i>Vitex doniana sweet</i> to identify potential inhibitors of thymidine kinase, the primary drug target of varicella zoster virus. Out of the 65 compounds docked, 42 of these compounds were observed to possess binding energies lower than −7.0 kcal/mol, however only 20 were observed to form hydrogen bond interactions with the protein. These interactions were elucidated using LigPlot<sup>+</sup> and MM-PBSA analysis with residue Ala134 predicted as critical for binding. Pharmacological profiling predicted three potential lead compounds comprising myricetin, apigenin- 4' -glucoside and Abyssinone V to possess good pharmacodynamics properties and negligibly toxic. The molecules were predicted as antivirals including anti-herpes and involved in mechanisms comprising inhibition of polymerase, ATPase and membrane integrity, which were corroborated previously in other viruses. These drug-like compounds are plausible biotherapeutic moieties for further biochemical and cell-based assaying to discover their potential for use against chickenpox. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16635406.v1
title: Identification of novel potential inhibitors of varicella-zoster virus thymidine kinase from ethnopharmacologic relevant plants through an <i>in-silico</i> approach

description: Although Varicella or chickenpox infection which is caused by the varicella-zoster virus (VZV) has significantly been managed through vaccination, it remains an infection that poses threats to the nearest future due to therapeutic drawbacks. The focus of this research was geared towards <i>in silico</i> screening for the identification of novel compounds in plants of ethnopharmacological relevance in the treatment of chicken pox in West Africa. The work evaluated 65 compounds reported to be present in <i>Achillea millefolium, Psidium guajava</i> and <i>Vitex doniana sweet</i> to identify potential inhibitors of thymidine kinase, the primary drug target of varicella zoster virus. Out of the 65 compounds docked, 42 of these compounds were observed to possess binding energies lower than −7.0 kcal/mol, however only 20 were observed to form hydrogen bond interactions with the protein. These interactions were elucidated using LigPlot<sup>+</sup> and MM-PBSA analysis with residue Ala134 predicted as critical for binding. Pharmacological profiling predicted three potential lead compounds comprising myricetin, apigenin- 4' -glucoside and Abyssinone V to possess good pharmacodynamics properties and negligibly toxic. The molecules were predicted as antivirals including anti-herpes and involved in mechanisms comprising inhibition of polymerase, ATPase and membrane integrity, which were corroborated previously in other viruses. These drug-like compounds are plausible biotherapeutic moieties for further biochemical and cell-based assaying to discover their potential for use against chickenpox. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16558988
title: Complete reconstruction of dasatinib unbinding pathway from c-Src kinase by supervised molecular dynamics simulation method; assessing efficiency and trustworthiness of the method

description: Over the past years, rational drug design has gained lots of attention since employing it gave the world targeted therapy and more effective treatment solutions. Structure-based drug design (SBDD) is an excellent tool in rational drug design that takes advantage of accurate methods such as unbiased molecular dynamics (UMD) simulation for designing and optimizing molecular entities by understanding the binding and unbinding pathways of the binders. Supervised molecular dynamics (SuMD) simulation is a branch of UMD in which long-duration simulations are turned into short simulations, called replica, and a specific parameter is monitored throughout the simulation. In this work, we utilized this strategy to reconstruct the unbinding pathway of the anticancer drug dasatinib from its target protein, the c-Src kinase. Several unbinding events with valuable details were achieved. Then, to assess the efficiency and trustworthiness of the SuMD method, the unbinding pathway was also reconstructed by conventional UMD simulation, which uncovered some of the limitations of this method, such as limited sampling of the active site and finding the metastable states in the unbinding pathway. Furthermore, in times like these, when the world is desperate to find treatments for the Covid-19 disease, we think these methods are of exceptional value. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16558988.v1
title: Complete reconstruction of dasatinib unbinding pathway from c-Src kinase by supervised molecular dynamics simulation method; assessing efficiency and trustworthiness of the method

description: Over the past years, rational drug design has gained lots of attention since employing it gave the world targeted therapy and more effective treatment solutions. Structure-based drug design (SBDD) is an excellent tool in rational drug design that takes advantage of accurate methods such as unbiased molecular dynamics (UMD) simulation for designing and optimizing molecular entities by understanding the binding and unbinding pathways of the binders. Supervised molecular dynamics (SuMD) simulation is a branch of UMD in which long-duration simulations are turned into short simulations, called replica, and a specific parameter is monitored throughout the simulation. In this work, we utilized this strategy to reconstruct the unbinding pathway of the anticancer drug dasatinib from its target protein, the c-Src kinase. Several unbinding events with valuable details were achieved. Then, to assess the efficiency and trustworthiness of the SuMD method, the unbinding pathway was also reconstructed by conventional UMD simulation, which uncovered some of the limitations of this method, such as limited sampling of the active site and finding the metastable states in the unbinding pathway. Furthermore, in times like these, when the world is desperate to find treatments for the Covid-19 disease, we think these methods are of exceptional value. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16616635.v1
title: Drug repositioning against COVID-19: a first line treatment

description: COVID-19 disease caused by the SARS-CoV-2 virus has shaken our health and wealth foundations. Although COVID-19 vaccines will become available allowing for attenuation of disease progression rates, distribution of vaccines can create other challenges and delays. Hence repurposed drugs against SARS-CoV-2 can be an attractive parallel strategy that can be integrated into routine clinical practice even in poorly-resourced countries. The present study was designed using knowledge of viral pathogenesis and pharmacodynamics of broad-spectrum antiviral agents (BSAAs). We carried out the virtual screening of BSAAs against the SARS-CoV-2 spike glycoprotein, RNA dependent RNA polymerase (RdRp), the main protease (Mpro) and the helicase enzyme of SARS-CoV-2. Imatinib (a tyrosine kinase inhibitor), Suramin (an anti-parasitic), Glycyrrhizin (an anti-inflammatory) and Bromocriptine (a dopamine agonist) showed higher binding affinity to multiple targets. Further through molecular dynamics simulation, critical conformational changes in the target protein molecules were revealed upon drug binding which illustrates the favorable binding conformations of antiviral drugs against SARS-CoV-2 target proteins. The resulting drugs from the present study in combination and in cocktails from the arsenal of existing drugs could reduce the translational distance and could offer substantial clinical benefit to decrease the burden of COVID-19 illness. This also creates a roadmap for subsequent viral diseases that emerge. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16785161
title: Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates

description: Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔS<sub>Vib</sub> in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16785161.v2
title: Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates

description: Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔS<sub>Vib</sub> in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.16785161.v1
title: Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates

description: Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔS<sub>Vib</sub> in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21740534
title: Original data - Ross et al. Horse Housing on Prince Edward Island, Canada: Attitudes and experiences related to keeping horses outdoors and in groups

description: Raw data
DOI: 10.6084/m9.figshare.21740534.v5
title: Original data - Ross et al. Horse Housing on Prince Edward Island, Canada: Attitudes and experiences related to keeping horses outdoors and in groups

description: Raw data
DOI: 10.6084/m9.figshare.21740534.v4
title: Original data - Ross et al. Horse Housing on Prince Edward Island, Canada: Attitudes and experiences related to keeping horses outdoors and in groups

description: Raw data
DOI: 10.5281/zenodo.7532870
title: Microbiome of domestic water in rainwater-harvesting dependent Carriacou, Grenada - Water_aCCSIS Project

description: Data files for the manuscript "The microbiome of domestic water in the rainwater harvesting-dependent island community of Carriacou, Grenada in the southern Caribbean"
DOI: 10.5281/zenodo.7532869
title: Microbiome of domestic water in rainwater-harvesting dependent Carriacou, Grenada - Water_aCCSIS Project

description: Data files for the manuscript "The microbiome of domestic water in the rainwater harvesting-dependent island community of Carriacou, Grenada in the southern Caribbean"
DOI: 10.5517/ccdc.csd.cc26kjfr
title: CCDC 2042634: Experimental Crystal Structure Determination

description: Related Article: Brahim El Bali, Mohammed Lachkar, Amani Direm, Esra Çetiner, Koray Sayin, Michal Dusek|2021|J.Mol.Struct.|1227|129576|doi:10.1016/j.molstruc.2020.129576
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.35078/sqoh92
title: Replication Data for: Ficha epidemiológica de localidade: Distrito: Pirapora | Município: Santa Fé de Minas

description: Levantamento Triatomínico com operações de campo ocorridas em Minas Gerais pela Superintendência de Campanhas de Saúde Pública (SUCAM) e FUNASA (Fundação Nacional de Saúde), no período de 1979 a 1999, objetivando a busca da presença de vetores da doença de Chagas ou de vestígios dessa presença. A partir dela são orientadas as operações com inseticida (pt) Triatomine survey with field operations carried out in Minas Gerais by the Public Health Campaigns Superintendence (SUCAM) and FUNASA (National Health Foundation), from 1979 to 1999, aiming to search for the presence of Chagas disease vectors or traces of that presence. From it, operations with insecticide are guided (en) Encuesta de triatominos con operaciones de campo realizada en Minas Gerais por la Superintendencia de Campañas de Salud Pública (SUCAM) y FUNASA (Fundación Nacional de Salud), de 1979 a 1999, con el objetivo de buscar la presencia de vectores de la enfermedad de Chagas o rastros de esa presencia. Desde ella se orientan las operaciones con insecticida (es)
DOI: 10.5281/zenodo.7277206
title: DATASET: Electric Potential Distribution Inside the Electrolyte During High Voltage Electrolysis

description: This project contains all the data shown in the figures of the manuscript (and the supporting information) entitled:<br> 'Electric Potential Distribution Inside the Electrolyte During High Voltage Electrolysis'<br> (doi:10.26434/chemrxiv-2022-nw4sp). The data to each figure is provided in a subfolder with further information.
DOI: 10.6084/m9.figshare.20332890.v6
title: Phylogenomic and phylogenetic datasets and trees

description: Phylogenomic and phylogenetic datasets and trees
DOI: 10.34740/kaggle/dsv/4847483
title: COVID Vaccination in World (updated daily)
DOI: 10.5281/zenodo.7534284
title: Sample intensity and contribution function data for demcmc

description: Sample intensity and contribution functions. The intensities are taken from a single pixel of a Hinode/EIS map. The contribution functions were calculated using Chianti 10.0.2, assuming a pre-calculated density from the intensities.
DOI: 10.5281/zenodo.7534283
title: Sample intensity and contribution function data for demcmc

description: Sample intensity and contribution functions. The intensities are taken from a single pixel of a Hinode/EIS map. The contribution functions were calculated using Chianti 10.0.2, assuming a pre-calculated density from the intensities.
DOI: 10.6084/m9.figshare.21896574
title: Supplementary Material for: Identification of a Novel <b><i>IQCE</i></b> Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7

description: <b><i>Introduction:</i></b> Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including <i>IQCE</i> gene. More precisely, loss-of-function of <i>IQCE</i> is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642). <b><i>Case Presentation:</i></b> A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic <i>IQCE</i> variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient. However, copy number variant (CNV) analysis from WES data, using ExomeDepth, revealed a novel, likely pathogenic large deletion involving <i>IQCE</i> genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2–18 of the gene. <b><i>Conclusion:</i></b> <i>IQCE</i> gene codes for a 695-amino acid protein located at the base of the primary cilia that positively regulates the Hedgehog signaling pathway. This case report represents the first description of a large deletion in <i>IQCE</i> and indicates that implementation of ExomeDepth in routine WES analysis can contribute valuable information toward elucidating the correct etiology of rare genetic diseases, increasing the diagnostic yield, and minimizing the need for additional tests.
DOI: 10.6084/m9.figshare.21896574.v1
title: Supplementary Material for: Identification of a Novel <b><i>IQCE</i></b> Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7

description: <b><i>Introduction:</i></b> Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including <i>IQCE</i> gene. More precisely, loss-of-function of <i>IQCE</i> is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642). <b><i>Case Presentation:</i></b> A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic <i>IQCE</i> variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient. However, copy number variant (CNV) analysis from WES data, using ExomeDepth, revealed a novel, likely pathogenic large deletion involving <i>IQCE</i> genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2–18 of the gene. <b><i>Conclusion:</i></b> <i>IQCE</i> gene codes for a 695-amino acid protein located at the base of the primary cilia that positively regulates the Hedgehog signaling pathway. This case report represents the first description of a large deletion in <i>IQCE</i> and indicates that implementation of ExomeDepth in routine WES analysis can contribute valuable information toward elucidating the correct etiology of rare genetic diseases, increasing the diagnostic yield, and minimizing the need for additional tests.