Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies

Mithun Rudrapal; Neelutpal Gogoi; Dipak Chetia; Johra Khan; Saeed Banwas; Bader Alshehri; Mohammed A Alaidarous; Umesh D Laddha; Shubham J Khairnar; Sanjay G Walode

doi:10.1016/j.sjbs.2021.12.018

Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies

Saudi J Biol Sci. 2022 Apr;29(4):2432-2446. doi: 10.1016/j.sjbs.2021.12.018. Epub 2021 Dec 13.

Authors

Mithun Rudrapal¹, Neelutpal Gogoi², Dipak Chetia², Johra Khan^{3

4}, Saeed Banwas^{3

4

5}, Bader Alshehri^{3

4}, Mohammed A Alaidarous^{3

4}, Umesh D Laddha⁶, Shubham J Khairnar⁶, Sanjay G Walode¹

Affiliations

¹ Department of Pharmaceutical Chemistry, Rasiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Chinchwad, Pune 411019, Maharashtra, India.
² Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam, India.
³ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
⁴ Health and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia.
⁵ Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA.
⁶ MET Institute of Pharmacy, Bhujbal Knowledge City, Adgaon, Nasik 422003, Maharashtra, India.

Abstract

In view of the potential of traditional plant-based remedies (or phytomedicines) in the management of COVID-19, the present investigation was aimed at finding novel anti-SARS-CoV-2 molecules by in silico screening of bioactive phytochemicals (database) using computational methods and drug repurposing approach. A total of 160 compounds belonging to various phytochemical classes (flavonoids, limonoids, saponins, triterpenoids, steroids etc.) were selected (as initial hits) and screened against three specific therapeutic targets (Mpro/3CLpro, PLpro and RdRp) of SARS-CoV-2 by docking, molecular dynamics simulation and drug-likeness/ADMET studies. From our studies, six phytochemicals were identified as notable ant-SARS-CoV-2 agents (best hit molecules) with promising inhibitory effects effective against protease (Mpro and PLpro) and polymerase (RdRp) enzymes. These compounds are namely, ginsenoside Rg2, saikosaponin A, somniferine, betulinic acid, soyasapogenol C and azadirachtin A. On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively. The present investigation can be directed towards further experimental studies in order to confirm the anti-SARS-CoV-2 efficacy along with toxicities of identified phytomolecules.

Keywords: Drug repurposing; Molecular docking; Molecular dynamics; Phytochemicals; Phytomedicine; SARS-CoV-2 infection.