tetano
Editor, Senior Moderator
F1000Res
. 2021 May 7;10:Chem Inf Sci-358.
doi: 10.12688/f1000research.52168.1. eCollection 2021.
Identification of potential inhibitors of SARS-CoV-2 S protein-ACE2 interaction by in silico drug repurposing
Fabiola E Tristán-Flores[SUP] 1 [/SUP], Diana Casique-Aguirre[SUP] 2 [/SUP], Raquel Pliego-Arreaga[SUP] 3 [/SUP], Juan A Cervantes-Montelongo[SUP] 4 [/SUP], Ponciano García-Gutierrez[SUP] 5 [/SUP], Gerardo Acosta-García[SUP] 4 [/SUP], Guillermo A Silva-Martínez[SUP] 4 6 [/SUP]
Affiliations
Abstract
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 (RBD [SUB]S1[/SUB])-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 RBD [SUB]S1[/SUB]-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.
Keywords: ACE2; COVID-19; Drug Repurposing; Molecular Docking; SARS-CoV-2.
. 2021 May 7;10:Chem Inf Sci-358.
doi: 10.12688/f1000research.52168.1. eCollection 2021.
Identification of potential inhibitors of SARS-CoV-2 S protein-ACE2 interaction by in silico drug repurposing
Fabiola E Tristán-Flores[SUP] 1 [/SUP], Diana Casique-Aguirre[SUP] 2 [/SUP], Raquel Pliego-Arreaga[SUP] 3 [/SUP], Juan A Cervantes-Montelongo[SUP] 4 [/SUP], Ponciano García-Gutierrez[SUP] 5 [/SUP], Gerardo Acosta-García[SUP] 4 [/SUP], Guillermo A Silva-Martínez[SUP] 4 6 [/SUP]
Affiliations
- PMID: 34900223
- PMCID: PMC8630554
- DOI: 10.12688/f1000research.52168.1
Abstract
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 (RBD [SUB]S1[/SUB])-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 RBD [SUB]S1[/SUB]-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.
Keywords: ACE2; COVID-19; Drug Repurposing; Molecular Docking; SARS-CoV-2.