Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro

Haixia Su; Sheng Yao; Wenfeng Zhao; Minjun Li; Jia Liu; Weijuan Shang; Hang Xie; Changqiang Ke; Meina Gao; Kunqian Yu; Hong Liu; Jingshan Shen; Wei Tang; Leike Zhang; Jianping Zuo; Hualiang Jiang; Fang Bai; Yan Wu; Yang Ye; Yechun Xu

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038687 doi: bioRxiv preprint determined by the CCK8 assay, and the resulting half-cytotoxic concentration (CC50) of the two compounds was over 200 μM, demonstrating a very low cytotoxicity of baicalin and baicalein (Fig. 3) . Subsequently, the Vero E6 cells were infected with SARS- CoV CoVs. The substrate specificity of 3CLpros is featured by the efficient cleavage in the peptides including (Leu,Phe,Met,Val)-Gln(Ser,Ala,Gly) sequences (the cleavage site is indicated by ), and the crystal structures have revealed a remarkable degree of conservation of the substrate-binding sites, particularly for the crucial S1/S2 subsites (7, 19, 20) . Accordingly, substrate analogs or mimetics attached with a chemical warhead targeting the catalytic cysteine were designed as peptidomimetic inhibitors of 3CLpros with a covalent mechanism of action (6). A series of diamide acetamides acting as non-covalent SARS-CoV 3CLpro inhibitors and their binding modes examined by crystal structures have been reported, but they are more or less peptidomimetic inhibitors and a continuous development of these compounds is absent author/funder. All rights reserved. No reuse allowed without permission.