Exploiting the antiviral properties of selected phytochemicals from leaf extracts of Spondias mombin (Linn): A computational repurposing approach toward the discovery of potential SARS-CoV-2 inhibitors.

Abstract

\n Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, remains a major public health concern that is causing tremendous human suffering. There is no approved drug for the direct treatment of the disease, although several vaccines have been approved for use. Exploring medicinal plants and their phytochemicals has emerged as possible therapeutic alternatives since they are affordable and present minimal toxicity effects. This study sought to investigate the potential of the phytochemical compounds isolated from ethanolic leaf extract of Spondias mombin as potential therapeutic agents against SARS-CoV-2. From a select list of bioactive compounds extracted from the leaf of Spondias mombin with known antiviral properties, we identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitors targeting SARS-CoV-2 RNA-dependent polymerase, the receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Analysis of the binding mechanism of these compounds is characterized by the formation of high-affinity intermolecular interactions with respective binding site residues of SARS-CoV-2 RNA-dependent polymerase, 3CLpro, and RBD of viral S-protein, which subsequently contributed to favourable binding affinity. Using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPB-SA) approach, Geraniin exhibited a binding free energy (ΔGbind) of -25.87kcal/mol and −\u200921.74kcal/mol, respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of -32kcal/mol towards 3CLpro. Molecular Dynamics (MD) simulations revealed crucial structural changes induced by the identified inhibitors, which possibly interfered with enzyme functions. The molecular insights provided regarding the inhibitory potency of the two phytochemicals warrants further experimental evaluation towards discovering novel SARS-CoV-2 therapeutics.