Virtual screening and molecular docking studies o certain lead-like compounds from ZINC15 database against COVID-19 Mpro enzyme Potential lead-like compounds against COVID-19 Mpro

ABSTRACT

Aim: The COVID-19 epidemic, which first emerged in Wuhan in December 2019, rapidly affected the globe in the form of a pandemic, and currently millions of people are classified as active cases in terms of this infection, while tens of thousands of people are in serious or critical conditions. Material and Methods: In this study, 100 lead-like chemical entities were downloaded from the ZINC15 database and subjected to structure-based virtual screening (SBVS) in terms of their potential to be used in combating COVID-19. In our molecular docking study, the Mpro (3CLpro) enzyme encoded by the COVID-19 genome was selected as the receptor molecule that could be targeted in the treatment. Results: A total of 3 small molecules (ZINC000000011271, ZINC000000026220 and ZINC000000006645) were identified as potential inhibitors due to their high binding affinities to this enzyme. Physicochemical profiles of the top-ranked ligands, determined in our study, showed that these compounds were safe and had drug-like features. Furthermore, in molecular dynamics (MD) simulations, the top-ranked compound ZINC000000011271 was found to strongly bound to the Mpro enzyme and preserved its hydrogen bonding stability throughout the whole trajectory. Discussion: In this study, three orphaned drugs (ZINC000000011271, ZINC000000026220 and ZINC000000006646) were found to strongly inhibit Mpro in molecular simulations. These compounds also displayed hit features according to the SwissADME database. Therefore, these hits defined in this study may be used In the development and advanced optimization of potent COVID-19 inhibitors.