Cribado virtual de inhibidores de la enzima Mpro del virus SARS-CoV-2 empleando librerías de compuestos y homología estructural con proteasas de virus patógenos humanos

Abstract

The present research project was carried out to find and develop ligands with inhibitory activity against the Mpro protease of the SARS CoV-2 virus through a virtual screening of recently developed inhibitors against this and those that have been previously tested in human pathogenic viruses. For which, compound libraries such as Protein Data Bank were used, from which 46 molecules with a high binding affinity to Mpro were chosen from a study of structural homology with the proteases of other viruses that attack humans and Covid Box. library that can be accessed from the following domain: https://www.mmv.org/mmv-open/covid-box from where a total of 79 molecules were taken, the selected ligands were presented as inhibitors of Mpro, at starting from the formation of hydrophobic, polar interactions and pi bonds between carbon - carbon, sulfur - carbon and fluorine - carbon atoms. To select the best molecules, a bioinformatic analysis was carried out in software such as Wincoot, Pymol and GOLD - Protein Ligand Docking Software, the latter for docking or molecular docking tests, studied at a conformational level by the arrangement and overlapping of atoms, level of incidence of intermolecular interactions and the possibility of steric shocks of their functional groups, obtaining as a result that the MMV1580167 molecule from Covid Box presents the best inhibitory activity within the virtual screening, while the designed AS7 ligand presents the highest inhibitory activity in the virtual environment where the investigation was carried out.