دورية أكاديمية
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase.
| العنوان: | Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase. |
|---|---|
| المؤلفون: | Zeng J; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Weissmann F; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Bertolin AP; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Posse V; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Canal B; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Ulferts R; Cell Biology of Infection Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Wu M; High Throughput Screening, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Harvey R; World Influenza Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Hussain S; World Influenza Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Milligan JC; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Roustan C; Structural Biology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Borg A; Structural Biology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., McCoy L; Division of Infection and Immunity, University College London, London WC1E 6BT, U.K., Drury LS; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Kjaer S; Structural Biology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., McCauley J; World Influenza Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Howell M; High Throughput Screening, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Beale R; Cell Biology of Infection Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K., Diffley JFX; Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K. |
| المصدر: | The Biochemical journal [Biochem J] 2021 Jul 16; Vol. 478 (13), pp. 2405-2423. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Print Cited Medium: Internet ISSN: 1470-8728 (Electronic) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society |
| مواضيع طبية MeSH: | Drug Evaluation, Preclinical*, Antiviral Agents/*chemistry , Antiviral Agents/*pharmacology , RNA Helicases/*antagonists & inhibitors , SARS-CoV-2/*enzymology , Small Molecule Libraries/*pharmacology , Viral Nonstructural Proteins/*antagonists & inhibitors, Animals ; Chlorocebus aethiops ; Enzyme Assays ; Fluorescence Resonance Energy Transfer ; High-Throughput Screening Assays ; RNA Helicases/metabolism ; Reproducibility of Results ; SARS-CoV-2/drug effects ; Small Molecule Libraries/chemistry ; Suramin/pharmacology ; Vero Cells ; Viral Nonstructural Proteins/metabolism |
| مستخلص: | The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterized pharmaceuticals for nsp13 inhibitors using a fluorescence resonance energy transfer-based high-throughput screening approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells. (© 2021 The Author(s).) |
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| فهرسة مساهمة: | Keywords: COVID-19; RNA helicase; coronavirus; nsp13 |
| المشرفين على المادة: | 0 (Antiviral Agents) 0 (Small Molecule Libraries) 0 (Viral Nonstructural Proteins) 6032D45BEM (Suramin) EC 3.6.4.13 (RNA Helicases) |
| تواريخ الأحداث: | Date Created: 20210701 Date Completed: 20210708 Latest Revision: 20210803 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8286831 |
| DOI: | 10.1042/BCJ20210201 |
| PMID: | 34198322 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1470-8728 |
|---|---|
| DOI: | 10.1042/BCJ20210201 |