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《ChemRxiv，2月11日，Prediction of the 2019-nCoV 3C-like Protease (3CLpro) Structure: Virtual Screening Reveals Velpatasvir, Ledipasvir, and Other Drug Repurposing Candidates》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-02-14

  • Prediction of the 2019-nCoV 3C-like Protease (3CLpro) Structure: Virtual Screening Reveals Velpatasvir, Ledipasvir, and Other Drug Repurposing Candidates

    Preprint submitted on 11.02.2020, 00:26 and posted on 11.02.2020, 11:48 by Yu Wai Chen Chin-Pang Yiu Kwok-Yin Wong

    We prepared the three-dimensional model of the 2019-nCoV 3C-like protease (3CLpro) using the crystal structure of the highly-similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are in the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its 2019-nCoV counterpart. With the 3CLpro molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the 2019-nCoV with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir / sofosbuvir) and Harvoni (ledipasvir / sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.

    *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.

  • 原文来源：https://chemrxiv.org/articles/Prediction_of_the_2019-nCoV_3C-like_Protease_3CLpro_Structure_Virtual_Screening_Reveals_Velpatasvir_Ledipasvir_and_Other_Drug_Repurposing_Candidates/11831103
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    • 编译者：zhangmin
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