Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection

• Published in: Phytomedicine Plus : International journal of phytotherapy and phytopharmacology Vol. 1; no. 4; p. 100135
• Main Authors: Oyedara, Omotayo O., Agbedahunsi, Joseph M., Adeyemi, Folasade M., Juárez-Saldivar, Alfredo, Fadare, Olatomide A., Adetunji, Charles O., Rivera, Gildardo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2021; The Author(s). Published by Elsevier B.V; Elsevier
• Subjects: ADMET; M. oleifera; Molecular docking; Phytochemical; SARS-CoV-2; TMPRSS2; HIA; BBB; TMPRSS2; RMSD; ADMET; Molecular docking; QMEAN; M. oleifera; COVID-19; LD50; SARS-CoV-2; HOB; GMQE; Phytochemical; CASTp; HOB, Human oral bioavailability; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; LD50, Lethal dose 50; RMSD, Root-mean-square deviation; COVID-19, Coronavirus Disease 2019; QMEAN, Qualitative Model Energy Analysis; HIA, Human intestinal absorption; BBB, Blood brain barrier; TMPRSS2, Transmembrane Protease Serine 2; CASTp, Computed atlas of surface topography of proteins; GMQE, Global quality estimation score; ADMET, Absorption, distribution, metabolism, excretion and toxicity
• ISSN: 2667-0313; 2667-0313
• DOI: 10.1016/j.phyplu.2021.100135

•Inhibition of TMPRSS2 from priming the Spike (S) protein prevents SARS-CoV-2 from entering into the human cell to cause COVID-19.•Phytochemicals that can inhibit the activity of TMPRSS2 are good drug candidates to treat SARS-CoV-2 infection.•Niazirin, quercetin, and moringyne from Moringa oleifera showed good properties as potential inhibitors of TMPRSS2. SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19. Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19. [Display omitted]