Computational bioprospection of selected plant secondary metabolites against VP7 (capsid protein) of rotavirus A

Abstract

Despite the global implementation of prequalified oral vaccines by the World Health Organization (WHO) in numerous countries, rotavirus A (RVA) have continued to be the principal cause of acute dehydrating diarrhoea in children under five years of age. Unfortunately, there are no authorized anti-rotaviral medications. Hence, it is crucial to prioritize the development of specialized therapeutics to combat rotaviral infections. For the first time, Spondias mombin, Macaranga barteri and Dicerocaryum eriocarpum metabolites were screened using computational techniques to identify potential novel modulators with broad-spectrum activity against VP7 epitopes (capsid protein) of RVA. Compounds with poor pharmacokinetics and drug-likeness were screened out from the initial top 20 metabolites identified using molecular docking. Thereafter, molecular dynamics (MD) simulation was used to assess the ability of the resulting compounds to modulate the selected VP7 epitopes. Remarkably, all the lead compounds had higher negative binding free energy than tizoxanide across the three epitopes of VP7, with apigenin-4′-glucoside having the highest affinity for VP7A (−24.13 kcal/mol) and VP7C (−43.67 kcal/mol) while the highest affinity for VP7D was observed in 2SG (−36.08 kcal/mol). Interestingly, 2SG (−18.24 kcal/mol, −31.21 kcal/mol, −36.08 kcal/mol), apigenin-4′-glucoside (−24.13 kcal/mol, −43.67 kcal/mol, −33.52 kcal/mol) and gnetin L (−21.21 kcal/mol, −27.56 kcal/mol, −32.48 kcal/mol) had better broad-spectrum affinities for VP7A, C and D relative to tizoxanide (−10.36 kcal/mol, −18.32 kcal/mol, −12.98 kcal/mol) respectively. Generally, the compounds are thermodynamically stable with 2SG (1.88 Å), ellagic acid (2.45 Å) and sericetin (2.22 Å) being the most stable against VP7A, C and D respectively. While this study unearths the lead compounds' promising ability to modulate the investigated VP7 epitopes, further confirmatory in vitro and in vivo studies are imperative, and efforts are underway towards achieving this task.

Keywords

• VP7 epitopes
• Capsid protein
• Binding free energy
• Thermodynamic stability
• Molecular dynamics simulation