Virtual screening for potential inhibitors of the molecular interaction of SARS‐CoV‐2 binding to the ACE2 receptor

Silva‐Martinez, Guillermo; Tristan‐Flores, Fabiola; Pineda‐Silva, Ruy; Acosta‐García, Gerardo; Pliego‐Arriaga, Raquel; Cervantes‐Montelongo, Juan; García‐Gutierrez, Ponciano; Casique‐Aguirre, Diana

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) appeared in Wuhan, China, in December 2019, causing COVID‐19 disease which are cases of SARS‐like atypical pneumonia. As of December 1, 2020, México had reached 1.1 million cases of COVID‐19 and 106 thousand deaths; about 63.6 million cases and 1.47 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. Rigid molecular docking was performed using RBD S(1) ‐ ACE2 (PDB: 6WV1) interaction site and 1,300 FDA approved and prescripted drugs by the Mexican Public Health System. The results were analyzed by docking score, frequency of the drug at receptor site and the types of interactions in the binding site residues. Within the top‐ranked drugs identified as a potentials inhibitor of RBD S1 ‐ ACE2 interaction we found pitavastatin, cholecalciferol, pargeverine, ipratropium, formoterol and fexofenadine, were the vast majority stands out as they are used as therapies to treat COPD, asthma and virtually any respiratory infection. Our results will serve as the basis for in vitro and in vivo studies to evaluate the potential use of these drugs to generate affordable an easily accessible therapies to treat COVID‐19.