Background: The recent outbreak caused by SARS-CoV-2, known as COVID-19, has been cataloged as a global catastrophe due to the growing number of infected cases and deaths since November 2019; this infectious, contagious disease, to date, does not have a vaccine or specific treatment available, which is why the number of cases continues to increase. SARS-CoV-2 infects humans as a result of the interaction between the receptor-binding domain of the viral spike protein and the receptor of the angiotensin-converting enzyme-2 (rACE2), located predominantly in the alveolar cells.
Objective: This study aims to identify inhibitory peptides of the protein-protein interaction between the receptor-binding-domain of the spike protein of SARS-CoV-2 and the angiotensin-converting enzyme-2 receptor through computational tools.
Methods: Through the Research Collaboratory for Structural Bioinformatics protein database, crystals were selected and interaction models were carried out between the viral protein and the ACE2; thereafter, the study designed inhibitory peptides of the interaction through the Rosetta web server, validated their interaction through ClusPro and, finally, determined the theoretical physicochemical and cytotoxic properties.
Results: A protein complex was generated and modeled through ClusPro; the balanced model was selected with the lowest binding energy. From the protein interactions of each of the crystals and from the model, eight peptides of 20 residues were obtained. The theoretical evaluation showed non-toxic peptides, six soluble in water, and two insoluble.
Conclusion: We found eight peptides that interacted with the receptor-binding-domain of the spike protein of SARS-CoV-2, which could avoid contact with the cell receptor and generate interference in the infection process.