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.