Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies
Authors
Mithun Rudrapal
aDepartment of Pharmaceutical Chemistry, Rasiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Chinchwad, Pune 411019, Maharashtra, India
Shubham Khairnar
fMET Institute of Pharmacy, Bhujbal Knowledge City, Adgaon, Nasik 422003, Maharashtra, India
Umesh Laddha
fMET Institute of Pharmacy, Bhujbal Knowledge City, Adgaon, Nasik 422003, Maharashtra, India
Mohammed Alaidarous
cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
Bader Alshehri
cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
Saeed Banwas
cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
Johra Khan
cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
Dipak Chetia
bDepartment of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam, India
Neelutpal Gogoi
bDepartment of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam, India
Sanjay Walode
aDepartment of Pharmaceutical Chemistry, Rasiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Chinchwad, Pune 411019, Maharashtra, India
Keywords:
SARS-CoV-2 infection, Phytomedicine, Molecular docking, Molecular dynamics, Phytochemicals, Drug repurposing
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: SARS-CoV-2 infection, Phytomedicine, Molecular docking, Molecular dynamics, Phytochemicals, Drug repurposing
Author Biographies
Mohammed Alaidarous, cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
dHealth and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia
Bader Alshehri, cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
dHealth and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia
Saeed Banwas, cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
eDepartment of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA
Johra Khan, cDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia
dHealth and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia
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