Targeting multiple SARS-CoV-2 domains by Indian medicinal plants – A Drug repurposing study using molecular docking, ADME-Tox analysis

Abstract

Abstract The rapid transmission of SARS-CoV-2 and its capability to spread in humans has brought about the development of new approaches for treatment against COVID-19. Drugs and vaccines available currently either target the virus ectodomain or endodomain. Thus, repurposing the use of natural products that target more than one part of the virus is the fastest option available for treatment. Plants are a repository of important constituents with proven significant efficacy against many human viruses. The present study focused on employing computational approaches for screening phytochemicals from 4 Indian medicinal plants, by targeting more than one part of SARS-CoV-2 for the identification of natural antiviral therapeutics to determine their feasibility as potential inhibitors of target viral proteins. Here, we used a multi-target, ligand virtual screening study on 9 target proteins important in SARS-CoV-2 lifecycle, namely Spike glycoprotein, Nucleocapsid phosphatase, Spike protein ACE-2, Non-structural protein 10 and 12, RdRp, Envelope protein, Main protease/3CL protease, and Papain like proteas. Out of the 58 plant phytochemicals screened, Z-5-methyl-6- heneicosen-11- one from Piper nigrum, Arjunetin from Terminalia arjuna, Rutin from Azadirachta indica and Makisterone A from Tinospora cordifolia exhibited highest binding affinity with 9 viral targets. In addition, ADMET analysis indicated Ursodeoxycholic acid, Ellagic Acid, Epicatechin and Isocolumbin, Ecdysterone, Columbin from Piper nigrum, Terminalia arjuna, Azadirachta indica, and Tinospora cordifolia have good binding energetics with the target viral proteins. The research thus enlightens the suitable pharmacological properties and the anti-viral activity of potential medicinal plant molecules for human administration using extensive in-silico techniques.