Biomaterial Database

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase. 2021

Quanjie Li, and Dongrong Yi, and Xiaobo Lei, and Jianyuan Zhao, and Yongxin Zhang, and Xiangling Cui, and Xia Xiao, and Tao Jiao, and Xiaojing Dong, and Xuesen Zhao, and Hui Zeng, and Chen Liang, and Lili Ren, and Fei Guo, and Xiaoyu Li, and Jianwei Wang, and Shan Cen

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.

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 corilagin as a medicinal herbal agent, these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.