Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

• 作者: Quanjie Li Dongrong Yi Xiaobo Lei Jianyuan Zhao Yongxin Zhang Xiangling Cui Xia Xiao Tao Jiao Xiaojing Dong Xuesen Zhao Hui Zeng Chen Liang Lili Ren Fei Guo Xiaoyu Li Jianwei Wang Shan Cen
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: Original articles
• 页码范围: 1555-1567
• 页数: 13页
• 语种: 英文

摘要

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health.The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals,whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus.Herein,we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp,binds directly to RdRp,effectively inhibits the polymerase activity in both cell-free and cell-based assays,fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50％ effective concentration (EC50) value of 0.13 μmol/L.Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp.In addition,combination of RAI-S-37 with remdesivir exhibits additive activity against anti-SARS-CoV-2 RdRp.Together with the current data available on the safety and pharmacokinetics of cor-ilagin as a medicinal herbal agent,these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.