The role of SARS-COV-2 -Main Protease: the case of Gepants family and Veruprevir
Keywords:
SARS-CoV-2, Docking analysis and GepantsAbstract
In this study, our approach was to conduct a complete investigation of molecular docking analysis with the major SARS-CoV-2 proteins and SARS CoV-1 proteins. We analyzed more than 6000 drugs, downloaded by the Pubchem database. Particular attention, we have focused on 3CLpro Covid-19 protein, by “Blind docking” method and “Selective docking” procedure, in Ligand Binding site, with Autodock Vina using Pyrx, a small Virtual Screen Library, and with Autodock 4 using AMDock Software. We have selected about 30 drugs with a high-affinity Binding score (between- 9.7 and-12 kcal/mol) from our results. Next, carrying out docking Validation methods, using Human Serum Albumin, as a docking control protein, has led us to select only the three best drugs (Ubrogepant, Atogepant, and Paritaprevir), potentially active in the Ligand Binding site pocket of 3CL-pro SARS-CoV-2 protein. Ubrogepant and Atogepant, have Ki values around, 20 -25 nM and Binding Energy of approximately -10 kcal/mol, except for Paritaprevir which reports exceptional Ki values of approximately 1nM and Binding Energy of approximately - 12.5 kcal/mol. This has led us to conclude, that they could be excellent candidates against SARS-COV-2, even though further in vitro and in vivo studies are needed.
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