Chinese scientists develop two novel compounds that inhibit SARS-CoV-2 main protease

Chinese scientists develop two novel compounds that inhibit SARS-CoV-2 main protease

Remdesivir drug stops novel coronavirus from replicating The results all showed that compounds 11a and 11b exhibited good anti-SARS-CoV-2-infection activity in cell culture (e.g., EC 50 values were 0.53 ± 0.01 μM and 0.72 ± 0.09 μM, respectively, when using the plaque assay). In addition, these compounds showed good PK properties in vivo, suggesting they are promising drug candidates. However, the lower toxicity of compound 11a makes it particularly promising. In order to elucidate the inhibition mechanism of SARS-CoV-2 M pro in compounds 11a and 11b, the scientists determined the high-resolution crystal structure of complexes M pro -11a (PDB: 6LZE) and M pro -11b (PDB: 6M0K) at 1.5-A resolution. The high-resolution crystal structure of these complexes not only demonstrated SARS-CoV-2 M pro -11a/11b interactions, but also revealed the mechanism of SARS-CoV-2 inhibition. High-resolution analysis of complexes is useful to medicinal chemists in designing novel inhibitors that act against SARS-CoV-2. This study shows that structure-based drug design is an effective strategy for designing specific antiviral leads against SARS-CoV-2. Preclinical research on compound 11a is now proceeding. The team has decided to share its research data with scientists around the world to accelerate the development of anti-SARS-CoV-2 drugs. In this study, the team led by Profs. LIU Hong, XU Yechun and JIANG Hualiang accomplished the design and synthesis of compounds and evaluated enzyme inhibitory activity; the team led by Profs. YANG Haitao and RAO Zihe determined the high-resolution crystal structure; and the team led by Profs. ZHANG Lei-Ke and XIAO Gengfu tested the antiviral activity. Source: Chinese Academy of Sciences Headquarters Journal reference: Dai, W., et al . (2020) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science . doi.



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