Exploration of alternate therapeutic remedies in Ebola virus disease: the case of reported antiviral phytochemical derived from the leaves Spondias Mombin Linn

Abstract

The most common and lethal of the six strains of Ebola viruses (EBOV) causing the Ebolavirus disease is the Zaire EBOV and has an approximately 90% mortality rate of infected patients. This study aimed to identify potential EBOV secreted Glycoprotein (sGP) inhibitors from reported phytochemical compounds with antiviral properties in leaf extracts of Spondias mombin Linn using computer-aided drug design approaches. Findings from the study indicated that Geraniin is the most promising inhibitor candidate, exhibiting the highest docking score of −\u20099.3\xa0kcal/mol with estimated binding free energy (ΔGbind) of −\u200930.34\xa0kcal/mol using Molecular Mechanics/Poisson–Boltzmann Surface Area approach after a 100\xa0ns Molecular Dynamic simulation was performed. The binding dynamics of Geraniin showed that there was an extensive network of interactions that anchored Geraniin within the EBOV sGP binding pocket accounting for the strong binding free energy. Crucial residues that interacted with Geraniin included; TRP104, ALA205, ARG136, ARG134, ASP208 and THR206. The pharmacokinetic analysis revealed that although Geraniin violated Lipinski’s rule of 5 typical of most natural compounds, the large molecular weight suggests that its synthetic fragmentation to smaller and simpler compounds could increase its bioactivity and pharmacokinetic features. In sum, a pharmacophore model generated showed that three aromatic rings, a hydrophobic ring and several hydrogen donors/acceptors on Geraniin were crucial towards its inhibitory binding on EBOV sGP. Therefore, subject to further experimental validation the insights provided in this report present Geraniin as a potential inhibitor candidate of EBOV sGP.