Department of Natural Sciences, Mars Hill University, Mars Hill, NC 28754, USA.
J Struct Biol. 2020 Sep 1;211(3):107575. doi: 10.1016/j.jsb.2020.107575. Epub 2020 Jul 10.
COVID-19 is a respiratory disease caused by the coronavirus SARS-CoV-2. SARS-CoV-2 has many similarities with SARS-CoV. Both viruses rely on a protease called the main protease, or M, for replication. Therefore, inhibiting M may be a successful strategy for treating COVID-19. Structures of the main proteases of SARS-CoV and SARS-CoV-2 with and without inhibitor N3 are available in the Protein Data Bank. Comparing these structures revealed residue interaction network changes associated with N3 inhibition. Comparing network clustering with and without inhibitor N3 identified the formation of a cluster of residues 17, 18, 30-33, 70, 95, 98, 103, 117, 122, and 177 as a network change in both viral proteases when bound to inhibitor N3. Betweenness and stress centrality differences as well as differences in bond energies and relative B-factors when comparing free M to inhibitor-bound M identified residues 131, 175, 182, and 185 as possibly conformationally relevant when bound to the inhibitor N3. Taken together, these results provide insight into conformational changes of betacoronavirus Ms when bound to an inhibitor.
新型冠状病毒病（COVID-19）是由冠状病毒 SARS-CoV-2 引起的呼吸道疾病。SARS-CoV-2 与 SARS-CoV 有许多相似之处。两种病毒都依赖一种称为主蛋白酶或 M 的蛋白酶进行复制。因此，抑制 M 可能是治疗 COVID-19 的一种有效策略。SARS-CoV 和 SARS-CoV-2 的主蛋白酶结构，无论是否有抑制剂 N3，都可在蛋白质数据库中获得。比较这些结构揭示了与 N3 抑制相关的残基相互作用网络变化。比较有和没有抑制剂 N3 的网络聚类，确定了在与抑制剂 N3 结合时，两个病毒蛋白酶中形成一个由残基 17、18、30-33、70、95、98、103、117、122 和 177 组成的残基簇的网络变化。当比较游离 M 与抑制剂结合的 M 时，介数和压力中心性差异以及键能和相对 B 因子的差异，确定残基 131、175、182 和 185 在与抑制剂结合时可能具有构象相关性。总之，这些结果提供了关于结合抑制剂时β冠状病毒 M 构象变化的见解。
