Virtual screening, MMGBSA, and molecular dynamics approaches for identification of natural products from South African biodiversity as potential Onchocerca volvulus pi-class glutathione S-transferase inhibitors

Mbah Bake Maraf; Bel Youssouf G Mountessou; Tsahnang Fofack Hans Merlin; Pouyewo Ariane; Joëlle Nadia Nouping Fekoua; Takoua Bella Jean Yves; Tchuifon Tchuifon Donald Raoul; Auguste Abouem A Zintchem; Gouet Bebga; Ndassa Ibrahim Mbouombouo; Ponnadurai Ramasami

doi:10.1016/j.heliyon.2024.e29560

Virtual screening, MMGBSA, and molecular dynamics approaches for identification of natural products from South African biodiversity as potential Onchocerca volvulus pi-class glutathione S-transferase inhibitors

Heliyon. 2024 Apr 18;10(9):e29560. doi: 10.1016/j.heliyon.2024.e29560. eCollection 2024 May 15.

Authors

Mbah Bake Maraf^{1

2}, Bel Youssouf G Mountessou², Tsahnang Fofack Hans Merlin^{3

4}, Pouyewo Ariane^{1

2}, Joëlle Nadia Nouping Fekoua^{1

2}, Takoua Bella Jean Yves², Tchuifon Tchuifon Donald Raoul⁵, Auguste Abouem A Zintchem², Gouet Bebga², Ndassa Ibrahim Mbouombouo^{2

6}, Ponnadurai Ramasami^{7

8}

Affiliations

¹ Physical and Theoretical Chemistry Unit, Laboratory of Applied Physical and Analytical Chemistry, Faculty of Science, University of Yaoundé I, P.O. BOX 812, Yaoundé, Cameroon.
² Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon.
³ Laboratoire Optique et Applications, Centre de Physique Atomique Moléculaire et Optique Quantique, Faculté des Sciences, Université de Douala, B.P. 8580, Douala, Cameroon.
⁴ Analytical, Structural and Materials Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Douala, B.P. 24157, Douala, Cameroon.
⁵ Department of Process Engineering, Laboratory of Energy, Materials, Modeling and Method, National Higher Polytechnic School of Douala, University of Douala, P.O. Box 2701 Douala, Cameroon, Douala.
⁶ Department of Applied Chemistry, Faculty of Science, University of Ebolowa, P.O. Box 118, Ebolowa, Cameroon.
⁷ Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, 80837, Mauritius.
⁸ Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, Doornfontein, 2028, South Africa.

Abstract

We investigated 1012 molecules from natural products previously isolated from the South African biodiversity (SANCDB, https://sancdb.rubi.ru.ac.za/), for putative inhibition of Onchocerca volvulus pi-class glutathione S-transferase (Ov-GST2) by virtual screening, MMGBSA, and molecular dynamics approaches. ADMET, docking, and MMGBSA shortlisted 12 selected homoisoflavanones-type hit molecules, among which two namely SANC00569, and SANC00689 displayed high binding affinities of -46.09 and -46.26 kcal mol-1, respectively towards π-class Ov-GST2, respectively. The molecular dynamics results of SANC00569 showed the presence of intermolecular H-bonding, hydrophobic interactions between the ligand and key amino acids of Ov-GST2, throughout the simulation period. This hit molecule had a stable binding pose and occupied the binding pockets throughout the 200 ns simulation. To the best of our knowledge, there is no report of any alleged anti-onchocerciasis activity referring to homoisoflavanones or flavonoids. Nevertheless, homoisoflavanones, which are a subclass of flavonoids, exhibit a plethora of biological activities. All these results led to the conclusion that SANC00569 is the most hypothetical Ov-GST2, which could lead the development of new drugs against Onchocerca volvulus pi-class glutathione S-transferase. Further validation of these ﬁndings through in vitro and in vivo studies is required.

Keywords: MMGBSA; Molecular dynamics; Onchocerca volvulus pi-class glutathione S-Transferase; South African natural products; Virtual screening.