Withania somnifera phytochemicals possess SARS-CoV-2 RdRp and human TMPRSS2 protein binding potential

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Research Articles | Published:

Print ISSN : 0970-4078.
Online ISSN : 2229-4473.
Pub Email: contact@vegetosindia.org
Doi: 10.1007/s42535-022-00404-4
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Keywords: SARS-CoV-2, Withania somnifera , Phytochemical, TMPRSS2, RNA dependent RNA polymerase


Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected approximately 26 million people and caused more than 6 million deaths globally. Spike (S)-protein on the outer surface of the virus uses human trans-membrane serine protease-2 (TMPRSS2) to gain entry into the cell. Recent reports indicate that human dipeptidyl peptidase-4 inhibitors (DPP4 or CD26) could also be utilized to check the S-protein mediated viral entry into COVID-19 patients. RNA dependent RNA polymerase (RdRp) is another key virulence protein of SARS-CoV-2 life cycle. The study aimed to identify the potential anti-SARS-CoV-2 inhibitors present in Withania somnifera (Solanaceae) using computer aided drug discovery approach. Molecular docking results showed that flavone glycoside, sugar alcohol, and flavonoid present in W. somnifera showed − 11.69, − 11.61, − 10.1, − 7.71 kcal/mole binding potential against S-protein, CD26, RdRp, and TMPRSS2 proteins. The major standard inhibitors of the targeted proteins (Sitagliptin, VE607, Camostat mesylate, and Remdesivir) showed the − 7.181, − 6.6, − 5.146, and − 7.56 kcal/mole binding potential. Furthermore, the lead phytochemicals and standard inhibitors bound and non-bound RdRp and TMPRSS2 proteins were subjected to molecular dynamics (MD) simulation to study the complex stability and change in protein conformation. The result showed energetically favorable and stable complex formation in terms of RMSD, RMSF, SASA, Rg, and hydrogen bond formation. Drug likeness and physiochemical properties of the test compounds exhibited satisfactory results. Taken together, the present study suggests the presence of potential anti-SARS-CoV-2 phytochemicals in W. somnifera that requires further validation in in vitro and in vivo studies.

              Withania somnifera
            , Phytochemical, TMPRSS2, RNA dependent RNA polymerase


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Author Information

Prajapati Kumari Sunita
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India

Singh Atul Kumar
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India

Kushwaha Prem Prakash
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India

Shuaib Mohd
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India

Maurya Santosh Kumar
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India

Gupta Sanjay
Department of Urology, Case Western Reserve University, Cleveland, USA

Senapati Sabyasachi
Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India

Singh Surya Pratap
Department of Bioscience and Biotechnology, Bansthali Vidyapith, Banasthali, India

Waseem Mohammad
Department of Zoology, Jagdam College, Jai Prakash University, Chapra, India

Kumar Shashank
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, India