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 |
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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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