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      An OpenData portal to share COVID-19 drug repurposing data in real time

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          Abstract

          The National Center for Advancing Translational Sciences (NCATS) has developed an online open science data portal for its COVID-19 drug repurposing campaign – named OpenData – with the goal of making data across a range of SARS-CoV-2 related assays available in real-time. The assays developed cover a wide spectrum of the SARS-CoV-2 life cycle, including both viral and human (host) targets. In total, over 10,000 compounds are being tested in full concentration-response ranges from across multiple annotated small molecule libraries, including approved drug, repurposing candidates and experimental therapeutics designed to modulate a wide range of cellular targets. The goal is to support research scientists, clinical investigators and public health officials through open data sharing and analysis tools to expedite the development of SARS-CoV-2 interventions, and to prioritize promising compounds and repurposed drugs for further development in treating COVID-19.

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          A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

          David E Gordon, Gwendolyn M Jang, Mehdi Bouhaddou … (2020)
          SUMMARY The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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            Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19

            Richard Eastman, Jacob Roth, Kyle R. Brimacombe … (2020)
            The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action—to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir’s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.
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              Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs

              Sangeun Jeon, Meehyun Ko, Jihye Lee … (2020)
              Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.
              Article 0 comments Cited 317 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): bioRxiv
                Journal ID (publisher-id): BIORXIV
                Title: bioRxiv
                Publisher: Cold Spring Harbor Laboratory
                Publication date (Electronic): 05 June 2020
                Electronic Location Identifier: 2020.06.04.135046
                Affiliations
                [1 ]National Center for Advancing Translational Sciences, National Institutes of Health
                Author notes
                [2]

                Contributed equally to this work.

                [3 ]Correspondence: Matthew Hall ( hallma@ 123456mail.nih.gov ) and Min Shen ( shenmin@ 123456mail.nih.gov )
                Article
                DOI: 10.1101/2020.06.04.135046
                PMC ID: 7276055
                PubMed ID: 32511420
                SO-VID: 5d13683f-f53e-46af-bd92-56a53d3d53f1
                License:

                It is made available under a CC-BY-NC-ND 4.0 International license.

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