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 S1)-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 S1-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.
Highlights
Emerging viruses can be defined as those whose incidence has increased in the last twenty years or whose presence has a high probability of increasing in the near future
Structural analysis of severe acute respiratory syndrome (SARS)-CoV-2 – angiotensin-converting enzyme 2 (ACE2) interaction The structural analysis for the SARS-CoV-2 RBDS1 of the spike protein in a complex with the ACE2 (PDB ID: 6VW1; Figure 1A) revealing a potential site for ligand binding inside ACE2 structure (Table 1)
The identified receptor site (Figure 1B) is proximal to the binding site of RBDS1 with a size of 86, it can be used for simulating rigid molecular docking since receptor atoms are in an exposed region of the structure, which could be in favor of drug binding
Summary
Emerging viruses can be defined as those whose incidence has increased in the last twenty years or whose presence has a high probability of increasing in the near future. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan, China, in December 2019, causing cases of SARS-like atypical pneumonia[5,6], with a clinical picture of fever, general malaise, dry cough, shortness of breath and was called the coronavirus disease 2019 (COVID-19)[7]. It can be asymptomatic, develop mild-to-severe symptoms, or cause death in elderly individuals or in patients with chronic diseases, such as hypertension, diabetes, and obesity[8]. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-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. Repurpose drugs targeting the angiotensin-converting enzyme 2 (ACE2) receptor represent an alternative strategy to block the binding of CoV2's protein S and forestall virus adhesion, internalization, and replication in the host cell
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