Inhibition of inosine monophosphate dehydrogenase in Lassa fever management by phenolics from (Telfairia Occidentalis ), an edible plant in Nigeria, using computational analysis

Abstract

Introduction: Lassa fever is an acute viral hemorrhagic fever caused by a single stranded RNA virus known as Lassa virus a member of the Arenaviridae family and it poses a significant health threat with increasing mortality rate and paucity of concrete evidence on the efficacy of the only available drug, Ribavirin. Methods: This study employed a comprehensive computational approach, including molecular docking, MMGBSA (Molecular Mechanics Generalized Born Surface Area), induced fit docking, and pharmacokinetic analysis, to identify phenolic compounds of Telfairia occidentalis leaves to target Inosine Monophosphate dehydreognase (IMPDH) protein for the development of potential therapies for Lassa fever. The crystallographic structure of Inosine Monophosphate Dehydrogenase (PDB ID: 1JR1) for Homo sapiens was retrieved from protein database repository (www.rcsb.org), the monomeric (chain A) protein was prepared using the protein preparation wizard of Schrodinger suit (2021 v2). The receptor grid generation tool of the software was used to generate a grid coordinate (1JR1: x = 66.56, y = 81.89, and z = 84.83) at the binding domain of the co crystalized ligand (phenolic acid). Results: Six (6) promising compounds were identified from phenolic compounds with better binding affinity with IMPDH ranging from 10.375 to 6.902 (kcal/mol) compared to Ribavirin, a standard drug ( 6.838 kcal/mol). The six compounds formed a stable complex with IMPDH protein and their predicted Half maximum inhibitory cocentration (IC50) ranged from 5.035 to 4.597, when compared with the standard drug Ribavirin with 3.404 value indicating the lead compounds’ bioactivity. Conclusion: The lead compounds passed Lipinski’s rule of five and have good pharmacokinetic properties. This study revealed the inhibitory potential of the compounds (Rutin, Isoquercetin, Myricetin, Luteolin, Quercetin and Catechin identified from phenolic compounds that can be exploited for the development of therapies for Lassa fever and other viral infections.