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

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

Automated summary

In this study, six phytochemicals and three drug compounds were analyzed for their potential as inhibitors against various drug targets of SARS-CoV-2 and human cellular proteins. The results showed that flabelliferin exhibited strong inhibitory effects on viral proteases, while nelfinavir was the most effective inhibitor against COVID-19 main protease. Flabelliferin also showed promising inhibitory effects on human cellular transmembrane serine proteinase. These findings suggest that these compounds could be potential therapeutics for COVID-19, but further clinical studies are required to confirm their efficacy.