Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing

Autor: Guillermo A Silva-Martínez, Ponciano García-Gutiérrez, Raquel Pliego-Arreaga, Fabiola E. Tristán-Flores, Diana Casique-Aguirre, Gerardo Acosta-García, Juan Antonio Cervantes-Montelongo
Rok vydání: 2021
Předmět:
0301 basic medicine
Drug
viruses
media_common.quotation_subject
ACE2
Pharmacology
medicine.disease_cause
General Biochemistry
Genetics and Molecular Biology
Protein S
Virus
03 medical and health sciences
0302 clinical medicine
In vivo
Humans
Medicine
030212 general & internal medicine
General Pharmacology
Toxicology and Pharmaceutics
media_common
Coronavirus
General Immunology and Microbiology
biology
SARS-CoV-2
business.industry
Drug Repositioning
COVID-19
virus diseases
Respiratory infection
Articles
General Medicine
biochemical phenomena
metabolism
and nutrition
digestive system diseases
Molecular Docking
Molecular Docking Simulation
Drug Repurposing
Drug repositioning
030104 developmental biology
Docking (molecular)
Spike Glycoprotein
Coronavirus
biology.protein
Angiotensin-Converting Enzyme 2
business
Research Article
Zdroj: F1000Research
ISSN: 2046-1402
Popis: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus discovered that appeared in Wuhan, China, in December 2019, causes COVID-19 disease which have resulted in cases similar to SARS-atypical pneumonia. As of March 1, 2021, Mexico had reached 2.11 million cases of COVID-19 and 189 thousand deaths; around 116 million cases and 2.57 million deaths are reported worldwide with new cases and increasing mortality every day. To date, there is no specific commercial treatment to control the infection. Repurpose drugs targeting the angiotensin-converting enzyme 2 (ACE2) receptor represents an alternative strategy to block the binding of SARS-CoV-2 protein S and forestall virus adhesion, internalization and replication in the host cell. Methods: Rigid molecular docking was performed using receptor binding domain of the S1 subunit of S protein (RBDS1)-ACE2 (PDB ID: 6VW1) interaction site and 1,283 drugs FDA approved and prescribed by the Mexican Public Health System. The results were analyzed by docking score, frequency of the drug in receptor site and the types of interactions at the binding site residues. Results: About 40 drugs were identified as a potential inhibitor of RBDS1-ACE2 interaction. Within the top-ranked drugs, we identified ipratropium, formoterol and fexofenadine, which stands out as they are used as therapies to treat chronic obstructive pulmonary disease, asthma and virtually any respiratory infection. Conclusions: Our results will serve as the basis for in vitro and in vivo studies to evaluate the potential use of those drugs to generate affordable and convenient therapies to treat COVID-19.
Databáze: OpenAIRE
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