Structure-guided discovery approach identifies potential lead compounds targeting M pro of SARS-CoV-2
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SHORT COMMUNICATION
Structure-guided discovery approach identifies potential lead compounds targeting Mpro of SARS-CoV-2 Mohcine Elmessaoudi-Idrissi1,2 • Kyoko Tsukiyama-Kohara3 • Jalal Nourlil4 • Anass Kettani2 • Marc P. Windisch5 • Michinori Kohara6 • Yashpal Singh Malik7 Kuldeep Dhama8 • Soumaya Benjelloun1 • Sayeh Ezzikouri1,3
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Received: 24 May 2020 / Accepted: 21 August 2020 Indian Virological Society 2020
Abstract 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 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13337-020-00627-6) contains supplementary material, which is available to authorized users. & Sayeh Ezzikouri [email protected] 1
Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc 1, Place Louis Pasteur, 20360 Casablanca, Morocco
2
Laboratoire de Biologie Et Sante´ (URAC34), De´partement de Biologie, Faculte´ Des Sciences Ben Msik, Universite´ Hassan II de Casablanca, Casablanca, Morocco
3
Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan
4
Medical Virology and BSL3 Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco
5
Applied Molecular Virology Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea
6
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
7
Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
8
Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
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), 60 -fluoroaristeromycin (ZINC000001483267) and cyclo (L-histidyl-L-histidyl) (ZINC000005116916) scaffolds. Further in vitro and in vivo validations are required to demonstrate anti-SARSCoV-2 activities. Keywords COVID-19 SARS-CoV-2 Therapy Protease Zinc Inhibitors In the late December 2019, hospitals in Wuhan, Hubei, China reported cases of unexplained pne
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