Molecular Insights on Bioactive Compounds against Covid-19: A Network Pharmacological and Computational Study

Abstract

Background: Network pharmacology based identification of phytochemicals in the form of cocktails against off-targets can play a significant role in the inhibition of SARS_CoV2 viral entry and its propagation. This study includes network pharmacology, virtual screening, docking and molecular dynamics to investigate the distinct antiviral mechanisms of effective phytochemicals against SARS_CoV2. Methods: SARS_CoV2 human-protein interaction network was explored from the BioGRID database and analysed using Cytoscape. Further analysis was performed to explore biological function, proteinphytochemical/ drugs network and up-down regulation of pathological host target proteins. This led to understand the antiviral mechanism of phytochemicals against SARS_CoV2. The network was explored through g: Profiler, EnrichR, CTD, SwissTarget, STITCH, DrugBank, BindingDB, STRING and SuperPred. Virtual screening of phytochemicals against potential antiviral targets such as M-Pro, NSP1, Receptor binding domain, RNA binding domain, and ACE2 discloses the effective interaction between them. Further, the binding energy calculations through simulation of the docked complex explain the efficiency and stability of the interactions. Results: The network analysis identified quercetin, genistein, luteolin, eugenol, berberine, isorhamnetin and cinnamaldehyde to be interacting with host proteins ACE2, DPP4, COMT, TUBGCP3, CENPF, BRD2 and HMOX1 which are involved in antiviral mechanisms such as viral entry, viral replication, host immune response, and antioxidant activity, thus indicating that herbal cocktails can effectively tackle the viral hijacking of the crucial biological functions of a human host. Further exploration through virtual screening, docking and molecular dynamics recognizes the effective interaction of phytochemicals such as punicalagin, scutellarin, and solamargine with their respective potential targets. Conclusion: This work illustrates a probable strategy for the identification of phytochemical-based cocktails and off-targets which are effective against SARS_CoV 2.