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

J Biomol Struct Dyn. 2022 Jul;40(11):5053-5059. doi: 10.1080/07391102.2020.1866669. Epub 2020 Dec 29.


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 3CLpro/Mpro), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV Mpro), SARS-CoV main proteinase (SARS CoV 3CLpro), 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.

MeSH terms

  • Antiviral Agents* / pharmacology
  • COVID-19 Drug Treatment
  • Coronavirus 3C Proteases* / antagonists & inhibitors
  • Curcumin* / pharmacology
  • Cysteine Endopeptidases / chemistry
  • Humans
  • Molecular Docking Simulation
  • Nelfinavir / pharmacology
  • Peptide Hydrolases
  • Phytochemicals* / pharmacology
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2* / drug effects
  • Viral Nonstructural Proteins / chemistry


  • Antiviral Agents
  • Phytochemicals
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Peptide Hydrolases
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases
  • Nelfinavir
  • Curcumin