Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase. Issue 13 (16th July 2021)

• Record Type: Journal Article
• Authors: Zeng, Jingkun; Weissmann, Florian; Bertolin, Agustina P.; Posse, Viktor; Canal, Berta; Ulferts, Rachel; Wu, Mary; Harvey, Ruth; Hussain, Saira; Milligan, Jennifer C.; Roustan, Chloe; Borg, Annabel; McCoy, Laura; Drury, Lucy S.; Kjaer, Svend; McCauley, John; Howell, Michael; Beale, Rupert; Diffley, John F.X.
• Is Part Of: Biochemical journal. Volume 478:Issue 13(2021)
• Page Start: 2405
• Page End: 2423
• Publication Date: 2021-07-16
• Subjects: coronavirus -- COVID-19 -- nsp13 -- RNA helicase; Biochemistry -- Periodicals; 572
• DOI: 10.1042/BCJ20210201
• Languages: English
• ISSNs: 0264-6021

Abstract

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.