Structure-guided discovery approach identifies potential lead compounds targeting Mpro of SARS-CoV-2

被引：3

作者：

Elmessaoudi-Idrissi M. ^{[1
,2
]}

Tsukiyama-Kohara K. ^{[3
]}

Nourlil J. ^{[4
]}

Kettani A. ^{[2
]}

Windisch M.P. ^{[5
]}

Kohara M. ^{[6
]}

Malik Y.S. ^{[7
]}

Dhama K. ^{[8
]}

Benjelloun S. ^{[1
]}

Ezzikouri S. ^{[1
,3
]}

机构：

[1] Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc 1, Place Louis Pasteur, Casablanca

[2] Laboratoire de Biologie Et Santé (URAC34), Département de Biologie, Faculté Des Sciences Ben Msik, Université Hassan II de Casablanca, Casablanca

[3] Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima

[4] Medical Virology and BSL3 Laboratory, Institut Pasteur du Maroc, Casablanca

[5] Applied Molecular Virology Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do

[6] Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo

[7] Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh

[8] Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh

来源：

VirusDisease | 2020年 / 31卷 / 4期

关键词：

COVID-19; Inhibitors; Protease; SARS-CoV-2; Therapy; Zinc;

D O I：

10.1007/s13337-020-00627-6

中图分类号：

学科分类号：

摘要：

The ongoing coronavirus disease 19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become fatal for the world with affected population crossing over 25 million in more than 217 countries, consequently declared a global pandemic by the World Health Organization. Unfortunately, neither specific prophylactic or therapeutic drugs nor vaccines are available. To address the unmet medical needs, we explored a strategy identifying new compounds targeting the main protease (Mpro) of SARS-CoV-2. Targeting the SARS-CoV-2 Mpro crystal structure (PDB ID: 6LU7) a combination of in silico screening, molecular docking, and dynamic approaches, a set of 5000 compounds of the ZINC database were screened. As a result, we identified and ranked the top 20 compounds based on the scores of ligand-interaction, their drug-likeness properties, and their predicted antiviral efficacies. The prominent drug-like and potent inhibitory compounds are 2-[2-(2-aminoacetyl) aminoacetyl] amino-3-(4-hydroxyphenyl)-propanamide (ZINC000004762511), 6′-fluoroaristeromycin (ZINC000001483267) and cyclo (L-histidyl-L-histidyl) (ZINC000005116916) scaffolds. Further in vitro and in vivo validations are required to demonstrate anti-SARS-CoV-2 activities. © 2020, Indian Virological Society.

引用

页码：549 / 553

页数：4

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