Abstract
SummaryThe 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 characterised pharmaceuticals for nsp13 inhibitors using a FRET-based high-throughput screening (HTS) 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.
Publisher
Cold Spring Harbor Laboratory
Reference68 articles.
1. World-Health-Organization. COVID19 - Numbers at a glance, https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed 28th February 2021.
2. Weisblum Y , Schmidt F , Zhang F , DaSilva J , Poston D , Lorenzi JC , et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020;9.
3. Genomic evidence for reinfection with SARS-CoV-2: a case study;Lancet Infect Dis,2021
4. Dai L , Gao GF . Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2020.
5. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity;Cell,2020
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献