Molecular Docking Analyses of Phytochemicals Obtained from African Antiviral Herbal Plants Exhibit Inhibitory Activity against Therapeutic Targets of SARS-CoV-2

Abstract

Presently, the global public health threat of international concern is the coronavirus disease-2019 (COVID-19), a viral disease of worldwide prevalence caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), at present the disease has no known cure or vaccine. Plants worldwide including plants of African ethnopharmacological relevance are a natural source of abundant and diverse phytochemicals with bioactivity against microorganisms including viruses. We selected 13 plants used in African traditional medicine for the treatment of viral diseases to screen for phytochemicals capable of interfering with SARS-CoV-2 therapeutic targets using AutoDock Vina in silico tool. 25 phytochemicals from these plants that passed the Lipinski rule of drug-likeness were assessed for antiviral activity against three SARS-CoV-2 therapeutic targets, namely: spike glycoprotein, Papain-like protease and 3C-like proteinase. The crystal structure of the viral protein targets was obtained from the protein databank website (https://www.rcsb.org/). The active sites of the target proteins were predicted using SCFBio Server (http://www.scfbio-iitd.res.in/dock/ActiveSite.jsp) from the PDB file as input. The antiviral herbal phytochemical compounds were then docked with prepared targets: Papain-like protease, 3C-like proteinase and spike glycoprotein. The Autodocking hit results generated six lead phytochemicals out of a library of twenty-five (25) phytochemicals from the African traditional herbs with potential anti-SARS-CoV-2 activity. The lead molecules with their binding affinities against Papain-like protease and 3C-Like Proteinase are as follows: Ginsenosides (-9.9 kcal/mol), ursolic acid (-9.4 kcal/mol), oleanolic acid (-9.4 kcal/mol), cynarine (-8.9 kcal/mol), glabridin (-8.5 kcal/mol) and cinnamoyl-echinadiol (-8.2 kcal/mol). ADMET profile shows glabridin, cinnamoyl-echinadiol and neral obtained from Licorice, Echinacea purpurea and lemongrass respectively, exhibited best-fit values as drugs candidate. We advocate for further in vitro and in vivo studies to evaluate the activity of these lead compounds with a view to optimized drug intervention against COVID-19 pandemic.

Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants

“…It is of interest that the high binding energies of 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside to ACE2 and TMPRSS2 could have clinical implication in the prevention of SARS-CoV-2 transmission [ 66 ]. Various studies have reported other phytomolecules present in African medicinal plants that have exhibited potential activity as antagonists against SARS-CoV-2 by interfering with different therapeutic targets [ 67 , 68 ]. These findings further buttress the role of NPs and their identified bioactives in tackling the COVID-19 pandemic.…”

Quantum Chemical Computations, Molecular Docking, and ADMET Predictions of Cynarin

“…Many studies have been conducted by researchers for cynarin, which has a wide range of biological activities: Some of these include janus kinase (JAK) inhibition [13], matrix metalloproteinase-9 (MMP-9) inhibition [14], spike (S) glycoprotein inhibition [15], inhibition on human colon cancer HT-29 and RKO. Cells [16], effects on inflammatory response in EA.hy926 human endothelial cells [17], and effects on amelanotic melanoma C32 and renal adenocarcinoma ACHN [18] have been reported.…”