Prospecção de inibidores enzimáticos para as proteínas Main Protease (MPRO) e Spike (S) do SARS-CoV-2 via método in sílico a partir de alcalóides derivados da Catharanthus roseus

Abstract

Since the advent of the COVID-19 pandemic, millions of people have died due to the worsening of the disease, which causes serious damage to the respiratory system. Although there are already several vaccines with proven efficacy, there is still an urgent need to develop drugs to combat this disease. The prospection of enzymatic inhibitors via in silico methods is an alternative of relevant scientific interest in the search for effective antiviral molecules. The present study aims to investigate the enzymatic inhibitory activity of the Main Protease (MPRO) and Spike (S) proteins of SARS-CoV-2 via in silico method using alkaloids derived from the plant Catharanthus roseus. The 3D structures of the ligands from Catharanthus roseus were obtained from the PubChem Open Chemistry Database, while the crystallographic structures of the MPRO (PDB ID: 6lu7) and S (PDB ID: 6slz) proteins were acquired from the Protein Data Bank. The molecular docking method was used to simulate the interactions between the binding molecules and the active sites of the target proteins. ADMET and toxicity studies of the main ligands that form enzymatic complexes were also carried out. The stability of the formed complexes was evaluated by identifying the Van der Waals interactions and hydrogen, enzymatic inhibition constants and binding Gibbs free energies. The main results suggest that strictosidine, isovincoside and bannucine molecules form enzymatic complexes with considerable chemical stability in relation to MPRO and Spike enzymes. ADMET tests were generally satisfactory for these binders. Therefore, it is suggested that these molecules have considerable anti-COVID-19 enzymatic inhibitory potential. These scientific findings are of relevant interest, given that they open the way for new in vitro and in vivo investigations in the prospection of new drugs to combat COVID-19.