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

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. Unfortu...

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Published in:Virusdisease 2020-12, Vol.31 (4), p.549-553
Main Authors: Elmessaoudi-Idrissi, Mohcine, Tsukiyama-Kohara, Kyoko, Nourlil, Jalal, Kettani, Anass, Windisch, Marc P., Kohara, Michinori, Malik, Yashpal Singh, Dhama, Kuldeep, Benjelloun, Soumaya, Ezzikouri, Sayeh
Format: Article
Language:English
Subjects:
Antiviral activity
Antiviral agents
Biochemistry
Biomedical and Life Sciences
Cell Biology
Coronaviruses
COVID-19
Crystal structure
Disease
Fatalities
Hydrogen
Life Sciences
Ligands
Microbiology
Pharmacokinetics
Pneumonia
Protein Structure
Severe acute respiratory syndrome coronavirus 2
Short Communication
Simulation
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Summary: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 (M pro ) of SARS-CoV-2. Targeting the SARS-CoV-2 M pro 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.
ISSN:2347-3584
2347-3517
DOI:10.1007/s13337-020-00627-6