Repurposing antiviral phytochemicals from the leaf extracts of Spondias mombin (Linn) towards the identification of potential SARSCOV-2 inhibitors

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, currently remains a significant public health concern causing tremendous human suffering. Although several approved vaccines exist, vaccine hesitancy, limited vaccine availability, high rate of viral mutation, and the absence of approved drugs account for the persistence of SARS-CoV-2 infections. The investigation of possibly repurposing of phytochemical compounds as therapeutic alternatives has gained momentum due to their reported affordability and minimal toxicity. This study investigated anti-viral phytochemical compounds from ethanolic leaf extracts of Spondias mombin L as potential inhibitor candidates against SARS-CoV-2. We identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitor candidates targeting the SARS-CoV-2 RNA-dependent polymerase receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Geraniin exhibited binding free energy (ΔGbind) of − 25.87 kcal/mol and − 21.74 kcal/mol towards SARS-CoV-2 RNA-dependent polymerase and receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of − 32 kcal/mol towards 3CLpro. Molecular Dynamics simulations indicated a possible interference to the functioning of SARS-CoV-2 targets by the two identified inhibitors. However, further in vitro and in vivo evaluation of these potential SARS-CoV-2 therapeutic inhibitor candidates is needed.

Spondias mombin: in Silico Screening of 1,2-Benzenedicarboxylic Acid, Butyl 2-Methylpropyl Ester (Fragment of Geraniin) as Anti-Marburg virus agent

“…In terms of Geraniin (98% w/w), we have reported in our previousin silico study to possess anti-Ebola and anti-SARS-CoV-2 properties against EBOV secreted Glycoprotein (sGP) and a possible inhibitor interferes with the functioning of SARS-CoV-2 targets (Boadu et al, 2022, Boadu et al, 2021. During the anti-Ebola study, a pharmacophore model generated showed that three aromatic rings, a hydrophobic ring and several hydrogen donors/acceptors were responsible for ant-Ebola activities, although it violated Lipinski's rule of five (Lipinski, Lipinski et al, 1997).…”