Abstract
The new outbreak of Coronavirus disease (COVID-19) has been entitled as a pandemic by W.H.O. It spreads to almost 211 countries due to its contagious nature. There is an urgent need for developing specific therapeutic agents against COVID-19. We have performed virtual screening of 52 ligands; most of which are essential components of traditional Ayurvedic medicine as well as natural compounds and three were standard repurposing drugs against COVID-19 Spike, Indian strain Spike (IS-Spike), PL-Pro and M-Pro to find potential inhibitor effects. Based on the docking results, it is estimated that compounds have a better binding affinity with M-Pro and PL-Pro than Spike as well as IS-Spike so it can be beneficial as therapeutics against COVID-19. We also conclude that the binding affinity of ligands with IS-Spike gets low as compared to Spike so the inhibitory potential of drugs may get weak. Based on the calculation of average binding energy (B.E) with the three targets, Spike, PL-Pro, and M-Pro, we found10 best ligands viz. (1) Punicafolin (2) Emblicanin A (3) Punigluconin (4) Lopinavir (5) Kuwanon X (6) Rutin (7) Lithospermic Acid (8) Phyllanemblinin A (9) Amarogentin and (10) Amaroswerin for inhibition. These ligands may act as potential inhibitors against COVID-19 druggable tri-targets. Network analysis revealed that four ligands out of 10 leading compounds are common in all four different networks (Spike, IS-Spike, PL-Pro, and M-Pro) which come under Phyllanthus emblica. Notably, a compound of Azadirachta indica out of 4 and a single compound of Swertia chirata was found common in all networks. Additionally, a standard drug Lopinavir and a compound of Salvia miltiorrhiza are frequently found in all networks. In principle, it appears plausible that the compounds which are common in the entire network should have more inhibitory potential against COVID19 due to the better binding potential among all targets, thus providing better candidacy for drug development.