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, Ciudad de México, Mexico.
J Comput Chem. 2021 May 15;42(13):897-907. doi: 10.1002/jcc.26512. Epub 2021 Mar 13.
SARS-CoV and SARS-CoV-2 belong to the subfamily Coronaviridae and infect humans, they are constituted by four structural proteins: Spike glycoprotein (S), membrane (M), envelope (E) and nucleocapsid (N), and nonstructural proteins, such as Nsp15 protein which is exclusively present on nidoviruses and is absent in other RNA viruses, making it an ideal target in the field of drug design. A virtual screening strategy to search for potential drugs was proposed, using molecular docking to explore a library of approved drugs available in the DrugBank database in order to identify possible NSP15 inhibitors to treat Covid19 disease. We found from the docking analysis that the antiviral drugs: Paritaprevir and Elbasvir, currently both approved for hepatitis C treatment which showed some of the lowest free binding energy values were considered as repositioning drugs to combat SARS-CoV-2. Furthermore, molecular dynamics simulations of the Apo and Holo-Nsp15 systems were performed in order to get insights about the stability of these protein-ligand complexes.
SARS-CoV 和 SARS-CoV-2 属于冠状病毒科，感染人类，它们由四种结构蛋白组成：刺突糖蛋白（S）、膜（M）、包膜（E）和核衣壳（N），以及非结构蛋白，如 Nsp15 蛋白，它仅存在于 nidoviruses 中，而不存在于其他 RNA 病毒中，使其成为药物设计领域的理想靶点。提出了一种虚拟筛选策略来寻找潜在药物，使用分子对接来探索 DrugBank 数据库中可用的已批准药物库，以确定可能的 NSP15 抑制剂来治疗 Covid19 疾病。我们从对接分析中发现，抗病毒药物：Paritaprevir 和 Elbasvir，目前均批准用于治疗丙型肝炎，它们显示出一些最低的自由结合能值，被认为是用于对抗 SARS-CoV-2 的重定位药物。此外，还对 Apo 和 Holo-Nsp15 系统进行了分子动力学模拟，以深入了解这些蛋白-配体复合物的稳定性。
