Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach

Abstract

In this work, Computer-aided drug design method has been implemented to quickly identify promising drug repurposing candidates against COVID-19. The world is facing an epidemic and in absence of vaccine or any effective treatment, it has created a sense of urgency for novel drug discovery approaches. We have made an immediate effort by performing virtual screening of clinically approved drugs or molecules under clinical trials against COVID-19 to identify potential drug molecules. With given knowledge of this system, N3 and 13B compounds have shown inhibitory effect against COVD-19. Both the compounds were considered as control to filter out the screened molecules. Overall, we have identified six potential compounds, Leupeptin Hemisulphate, Pepstatin A, Nelfinavir , Birinapant, Lypression and Octeotide which have shown the docking energy > -8 kcal/mol and MMGBSA > -90 kcal/mol. The binding pattern of these compounds suggests that they interact with key hot-spot residues. Also, the pharmacokinetic annotations and their biological activity have indicated that they possess drug-like properties and pave their way for in vitro studies The findings of this work will be significant for structure and pharmacophore-based designing