Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicaseMore about Open Access at the Crick
Authors listJingkun Zeng Florian Weissmann Agostina Bertolin Viktor Posse Berta Canal Rachel Ulferts Mary Wu Ruth Harvey Saira Hussain Jennifer Milligan Chloe Roustan Annabel Borg Laura McCoy Lucy Drury Svend Kjaer John Mccauley Michael Howell Rupert Beale John Diffley
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.
Journal Biochemical Journal
Issue number 13