Avaliação molecular in silico de fármacos antivirais comerciais para inibição da estrutura da protease principal do Sars-Cov-2

Abstract

This work aims at the molecular evaluation of antiviral compounds commercially used to inhibit the COVID-19 virus protein through computational techniques. Little is known about the interactive sites of the main protease of SARS-CoV-2, therefore, a computational investigation can bring crucial information about the regions of the protein that can be inhibited with drugs. At first, known and commercially sold antiviral agents were investigated, such as: Baloxavir marboxil (Xofluza), Oseltamivir (Tamiflu) and Zanamivir (Relenza). From a scientific point of view, these antiviral drugs are innocuous against the virus, however, molecular modifications in them may result in structures that are more attractive and active in inhibiting the virus. This molecular engineering can be easily proposed using computer programs, which make the desired molecular design. Experimentally, the viability of these changes in drugs needs to be verified, with collaborations with experimental groups being of fundamental importance. For this study, the target macromolecule will be the main protease of SARS-CoV-2, available in the protein repository (PDB ID: 6Y2F). The obtained positions of the ligands were submitted to simulations by molecular dynamics (DM) to balance the system. Based on the results obtained in this work, it is concluded that the drugs Baloxavir, Oseltamivir and Zanamivir showed greater affinities with the selected proteins, with binding energy values below -8.0 kcal/mol. Therefore, the repositioning or replacement of pre-selected functional groups of the analyzed drugs may be an alternative for the treatment of Covid-19, as the molecular affinity of the drugs with the virus proteins obtained satisfactory results.