Computational Insights of phytochemical Driven Disruption of RNA dependent RNA polymerase Mediated replication of Coronavirus: A Strategic Treatment Plan against COVID-19.

Current pandemic of COVID-19 caused by SARS-CoV-2 has raised global health concerns. RNA dependent RNA polymerase (RdRp) is the prime component of viral replication/proliferation machinery and is considered to be a potential drug target against SARS-CoV-2. Present study investigated the anti-RdRp activity of phytochemicals against SARS-CoV-2 infection. Virtual ligand screening was carried out to determine the potent compounds against RdRp. Molecular docking and MD Simulation study was employed to evaluate the spatial affinity of selected phytochemicals for the active sites of RdRp. Structural stability of target compounds was determined using RMSD computational analysis and drug like abilities were investigated using ADMET. Bond distance between ligand and receptor were marked to predict the strength of interaction. Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same. All the natural metabolites exhibited stable conformation during MD Simulation of 101ns at 310K. Kinetic, potential and electrostatic energy were observed to be least in case of natural metabolites in comparison to synthetic analogs. Deviation and fluctuations were observed to be structurally least in target phytochemicals. Physiochemical and biological properties of these compounds further validated their drug like properties. Non-bonded distance was found to be short enough to form hydrogen bonding or hydrophobic interactions which revealed that these target compounds can strongly bind with RdRp. The study brings forth the potential phytochemicals to disrupt the replication domain of SARS-CoV-2 by hindering RdRp. We therefore anticipate that the current findings could be considered as valuable for development of an efficient preventive/therapeutic expedient against COVID-19.