Reckoning γ-Glutamyl-S-allylcysteine as a potential main protease (mpro) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation
Authors
Arun Parashar
aFaculty of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, India
Arpit Shukla
bDepartment of Biological Sciences, Institute of Advanced Research, Gandhinagar, India
Ankush Sharma
dDepartment of Biotechnology, Yeshiva University, New York, NY, USA
Tapan Behl
eDepartment of Pharmacology, Chitkara University, Punjab, India
Dweipayan Goswami
fDepartment of Pharmacology, Govt. College of Pharmacy, Rohru, India
Vineet Mehta
eDepartment of Pharmacology, Chitkara University, Punjab, India
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19), outbreak was first reported in December 2019 in the Wuhan, China. COVID-19 managed to spread worldwide and so far more than 9.1 million cases and more than 4.7 lakh death has been reported globally. Children, pregnant women, elderly population, immunocompromised patients, and patients with conditions like asthma, diabetes, etc. are highly vulnerable to COVID infection. Currently, there is no treatment available for COVID-19 infection. Traditional medicinal plants have provided bioactive molecules in the past that are efficiently used during conditions like cancer, malaria, microbial infections, immune-compromised states, etc. AYUSH India has recommended the use of Curcuma longa, Allium sativum, Ocimum tenuiflorum, and Withania somnifera for immune-boosting during SARS-CoV-2 infection. In the present study, we investigated the potential of 63-major bioactive molecules of these plants against SARS-CoV-2 main protease (Mpro) through docking studies and compared the results with known inhibitor 11a. Our results proposed cuscohygrine, γ-Glutamyl-S-allylcysteine, anahygrine, and S-allylcystein as the potent inhibitors against Mpro identified using molecular docking and molecular simulation dynamics. Interestingly, these molecules are from A. sativum, and W. somnifera, which are known for their antimicrobial and immunomodulatory potential. None of the proposed molecules have earlier been reported as antiviral molecules. Our results predict very strong potential of these four-molecules against SARS-CoV-2 Mpro, especially γ-glutamyl-S-allylcysteine, as all four form hydrogen bonding with Glu166 that is a crucial residue for the formation of the biologically active dimeric form of Mpro. Therefore, we strongly recommend further research on these biomolecules against SARS-CoV-2.
Keywords: Molecular docking, COVID-19, SARS-CoV-2, coronavirus, allium sativum, withania somnifera
Author Biography
Arpit Shukla, bDepartment of Biological Sciences, Institute of Advanced Research, Gandhinagar, India
cDepartment of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, India
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