Zeng, J;
Weissmann, F;
Bertolin, AP;
Posse, V;
Canal, B;
Ulferts, R;
Wu, M;
... Diffley, JFX; + view all
(2021)
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase.
Biochemical Journal
, 478
(13)
pp. 2405-2423.
10.1042/BCJ20210201.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1042/BCJ20210201 |
| Publisher version: | https://doi.org/10.1042/BCJ20210201 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | COVID-19, RNA helicase, coronavirus, nsp13, Animals, Antiviral Agents, Chlorocebus aethiops, Drug Evaluation, Preclinical, Enzyme Assays, Fluorescence Resonance Energy Transfer, High-Throughput Screening Assays, RNA Helicases, Reproducibility of Results, SARS-CoV-2, Small Molecule Libraries, Suramin, Vero Cells, Viral Nonstructural Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10131507 |
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