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《BioRxiv，3月8日，Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-03-09

  • Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design

    Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, Rolf Hilgenfeld, Marcin Drag

    doi: https://doi.org/10.1101/2020.03.07.981928

    Abstract

    In December 2019, the first cases of a novel coronavirus infection were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for COVID-19, therefore research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 Mpro protease constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position.

    *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://www.biorxiv.org/content/10.1101/2020.03.07.981928v1
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    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-04-25
    • Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors Linlin Zhang1,2, Daizong Lin1,3, Xinyuanyuan Sun1,2, Ute Curth4, Christian Drosten5, Lucie Sauerhering6,7, Stephan Becker6,7, Katharina Rox8,9, Rolf Hilgenfeld1,2,* See all authors and affiliations Science 24 Apr 2020: Vol. 368, Issue 6489, pp. 409-412 DOI: 10.1126/science.abb3405 Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
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  • 《3月8日_SARS-CoV-2主蛋白酶Mpro的底物特异性谱为抗COVID-19药物设计提供了基础》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-03-10
    • 3月8日_SARS-CoV-2主蛋白酶Mpro的底物特异性谱为抗COVID-19药物设计提供了基础 1.时间：2020年3月8日 2.机构或团队：波兰弗罗茨瓦夫科技大学、德国吕贝克大学 3.事件概要： bioRxiv预印平台于2月8日发布了波兰弗罗茨瓦夫科技大学和德国吕贝克大学的论文“Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design”，文章称目前尚无针对COVID-19的有效抗病毒治疗，研究工作集中在疫苗和抗病毒药物的快速开发上。SARS-CoV-2 Mpro蛋白酶是最具吸引力的抗病毒药物靶标之一。为了解决这个新出现的问题，研究人员合成了在P1位点带有谷氨酰胺的荧光底物的组合库。研究人员利用该组合其使用天然和大量非天然氨基酸来确定SARS-CoV和SARS-CoV-2蛋白酶的底物偏好。研究人员称其工作结果为设计抑制剂作为抗病毒剂或诊断测试提供了结构框架。 *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。 4.附件： 原文链接：https://www.biorxiv.org/content/10.1101/2020.03.07.981928v1
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