An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study
An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study
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DOI：
10.1080/07391102.2020.1763201
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发表时间：
2020-05-11
影响因子：
4.4
通讯作者：
Singha Roy, Atanu
中科院分区：
文献类型：
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作者：
Das, Sourav;Sarmah, Sharat;Singha Roy, Atanu
世界卫生组织（世卫组织）最近宣布，由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的一种影响数百万人的新型传染病的新菌株为大流行病。目前，正在进行几项临床试验，以确定治疗这种新型病毒的特定药物。抑制SARS-CoV-2主要蛋白酶对于阻断病毒复制是必要的。本研究采用盲法分子对接的方法，从天然产物、抗病毒药物、抗真菌药物、抗线虫药物和抗原虫药物等共33种药物中筛选出SARS-CoV-2主要蛋白酶的抑制剂。所有被研究的分子都能与SARS-CoV-2蛋白酶（PDB：6Y84）的活性位点结合，其中芦丁（天然化合物）在所研究的33种分子中具有最高的抑制效率，其次是利托那韦（对照药物）、依地那韦（抗原虫药物）、橙皮苷（天然化合物）、洛匹那韦（对照药物）和茚地那韦（抗病毒药物）。所有的分子，在这里研究可以结合附近的关键催化残基，HIS 41和CYS145的主要蛋白酶，分子被包围的其他活性位点残基，如MET 49，GLY 143，HIS 163，HIS 164，GLU 166，PRO 168，和GLN 189。由于这项研究是基于分子对接，因此特别是所获得的结果，需要在体外和体内条件下进行广泛的湿实验室实验和临床试验。作者：Ramaswamy H. Sarma
A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions. Communicated by Ramaswamy H. Sarma