Metabolites profiling and molecular docking identification of putative leads from endophytic Phyllosticta capitalensis as modulators of key druggable structural targets of rotavirus A

Abstract

Rotavirus-induced gastroenteritis is a global health concern and the leading cause of death in low-income countries and children under the age of five. While rotavirus A (RVA) vaccines are available, there accessibility and efficacy remain challenging, especially in the third world countries. This has necessitated the need to develop therapeutics to manage RVA infection. This study investigated gas chromatography-mass spectrometry-derived Phyllosticta capitalensis metabolites as potential therapeutics against the key structural proteins [VP8* portion of the VP4 (spike protein), the VP7 (capsid protein), and the VP1 (RNA-dependent RNA polymerase)] of RVA using molecular docking and ADME approaches. The results revealed that four [lup-20(29)-en-one, A’-neogammacer-22(29)-ene, stigmasta-4,7,22-trien-3-α-ol, and fucosterol] of the 67 metabolites had favourable affinity for the three structural proteins and belonged to classes of metabolite of antiviral importance. Further analysis and pharmacokinetic profiling showed that the pentacyclic triterpenoids, lup-20(29)-en-one and A’-neogammacer-22(29)-ene, had the potential to be developed as antivirals against RVA infection and effort is underway in this direction.

Keywords:

• Anti-rotavirus metabolites
• Molecular docking
• Pharmacokinetics
• Rotavirus
• Structural proteins

ACKNOWLEDGEMENTS

The authors specially acknowledge the financial assistance of the Directorate of Research and Postgraduate Support, Durban University of Technology, South Africa.