Background In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. Results We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PL pro ). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CL pro ) in addition to PL pro . A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CL pro and PL pro . Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. Conclusions Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.
【저자키워드】 SARS-CoV-2, natural product, Anacardic acid, ginkgolic acid, Papain‐like protease, 【초록키워드】 antivirals, 3CL pro, protease, in vitro, Replication, Papain-like protease, inhibitor, mechanism of action, compounds, enzyme, Compound, concentrations, Result, develop, addition, characterized, provide, demonstrated, inhibit SARS-CoV-2, nontoxic, the SARS-CoV-2, 【제목키워드】 inhibitors of SARS-CoV-2, cysteine protease,