Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón S/N, Casco de Santo Tomás, 11340, Mexico, Mexico.
CNRS, Laboratoire de Chimie Théorique, LCT, Sorbonne Université, Paris, France.
Sci Rep. 2021 Feb 25;11(1):4659. doi: 10.1038/s41598-021-84053-8.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus responsible for coronavirus disease 2019 (COVID-19); it become a pandemic since March 2020. To date, there have been described three lineages of SARS-CoV-2 circulating worldwide, two of them are found among Mexican population, within these, we observed three mutations of spike (S) protein located at amino acids H49Y, D614G, and T573I. To understand if these mutations could affect the structural behavior of S protein of SARS-CoV-2, as well as the binding with S protein inhibitors (cepharanthine, nelfinavir, and hydroxychloroquine), molecular dynamic simulations and molecular docking were employed. It was found that these punctual mutations affect considerably the structural behavior of the S protein compared to wild type, which also affect the binding of its inhibitors into their respective binding site. Thus, further experimental studies are needed to explore if these affectations have an impact on drug-S protein binding and its possible clinical effect.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种新出现的冠状病毒，可引发 2019 年冠状病毒病（COVID-19）；自 2020 年 3 月以来，它已在全球范围内传播。迄今为止，已描述了在全球范围内流行的 SARS-CoV-2 的三个谱系，其中两个在墨西哥人群中发现，在这些谱系中，我们观察到位于氨基酸 H49Y、D614G 和 T573I 的刺突（S）蛋白的三个突变。为了了解这些突变是否会影响 SARS-CoV-2 的 S 蛋白的结构行为，以及与 S 蛋白抑制剂（蛇根碱、奈非那韦和羟氯喹）的结合，进行了分子动力学模拟和分子对接。结果发现，与野生型相比，这些定点突变会极大地影响 S 蛋白的结构行为，这也会影响其抑制剂与其各自结合位点的结合。因此，需要进一步的实验研究来探讨这些影响是否会对药物-S 蛋白结合及其可能的临床效果产生影响。
