Paromomycin: A Potential Dual Targeted Drug Effectively Inhibits both Spike (S1) and Main Protease of COVID-19

Abstract

With increase in number of people suffering from COVID-19, there is a dire need to look for effective remedies against this pandemic. Several different approaches are being investigated for fighting against this virus. In this study, we propose a single drug Paromomycin against two targets of COVID-19 i.e. Spike protein (S1) and protease domain. In our quest for finding potentialdrug against this virus, we have docked 2413 FDA approved drugs against protease and spike proteins of COVID-19. Based upon their glide scores, Paromomycin was found to have strong binding affinity against both the targets of coronavirus. To further elucidate, MD simulation of both docked complexes was performed. RMSD and energy plots in comparison to the PDB backbone of proteins without ligands were calculated which further confirmed the stability of the complexes.In addition to these drugs,15 anti-malarial drugs including chloroquine were also investigated against both targets using in-silico approach. It has been observed that no anti-malarial drug showed effective binding against either S1 or protease targets. Current study concluded that Paromomycin is an effective double target drug against coronavirus, as it binds not only to the protease domain of the virion but also with the spike domain with high stability.