In silico analysis of phytochemicals as potential inhibitors of proteases involved in SARS-CoV-2 infection

Abstract

In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CL^pro/M^pro), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV M^pro), SARS-CoV main proteinase (SARS CoV 3CL^pro), and one human cellular transmembrane serine proteinase (TMPRSS2), was carried out. Except leucoanthocyanin all other phytochemicals proved better than all three positive control drugs against SARS-CoV main peptidase, whereas, flabelliferin was found to be the potential inhibitor for SARS-CoV main proteinase out performing all the positive control drugs and phytochemicals. Amongst the compounds studied, the best inhibitor for COVID-19 main protease was nelfinavir followed by flabelliferin and ocimin. Flabelliferin was found to the best promising inhibitor of human cellular transmembrane serine proteinase, followed by nelfinavir, curcumin, piperine and marmelosin. The result on the inhibition of human cellular transmembrane serine proteinase against COVID-19 has a stable therapeutic advantage as mutation may quickly occur on viral drug targets. Hence, all the phytochemicals tested in the present study are the potential inhibitors of the all the four drug targets and can form a part of therapeutics against COVID-19 with further clinical studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19 main protease
• SARS-CoV main peptidase
• SARS-CoV main proteinase
• TMPRSS2
• drug likeliness

Acknowledgements

SM acknowledges Central University of Tamil Nadu, PU, MF &SS acknowledge Head, Division of Crop Improvement & Biotechnology & Dr. Nirmal Babu, Former Director ICAR – Indian Institute of Spices Research for the support. We also thank the anonymous reviewers for their suggestions which helped to improve the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.