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《Science，4月22日，Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-04-23

  • Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

    Wenhao Dai1,2,*, Bing Zhang4,*, Haixia Su1,*, Jian Li1,5, Yao Zhao3, Xiong Xie1, Zhenming Jin1, Fengjiang Liu3, Chunpu Li1, You Li6, Fang Bai3, Haofeng Wang3, Xi Cheng1, Xiaobo Cen6, Shulei Hu1, Xiuna Yang3, Jiang Wang1, Xiang Liu7, Gengfu Xiao4, Hualiang Jiang1,2,3, Zihe Rao3, Lei-Ke Zhang4,†, Yechun Xu1,†, Haitao Yang3,†, Hong Liu1,2,5,†

    See all authors and affiliations

    Science 22 Apr 2020:

    eabb4489

    DOI: 10.1126/science.abb4489

    Abstract

    SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (Mpro) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates.

  • 原文来源：https://science.sciencemag.org/content/early/2020/04/21/science.abb4489
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