Crystal Structure Of Sars-Cov-2 Main Protease In Complex With The Non-Covalent Inhibitor Ml188
VIRUSES-BASEL(2021)
摘要
Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M-pro) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M-pro, and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 M-pro at 2.5 mu M, which is more potent than against SAR-CoV-1 M-pro. We determined the crystal structure of ML188 in complex with SARS-CoV-2 M-pro to 2.39 angstrom resolution. Sharing 96% sequence identity, structural comparison of the two complexes only shows subtle differences. Non-covalent protease inhibitors complement the design of covalent inhibitors against SARS-CoV-2 main protease and are critical initial steps in the design of DAAs to treat CoVID 19.
更多查看译文
关键词
SARS-CoV-2, Covid-19, main protease, M-pro, ML188, protease inhibitor, crystal structure, structure-based drug design, direct-acting antivirals
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要