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

Heliyon (May 2024)

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

Affiliations

Mbah Bake Maraf: 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; Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon; Corresponding author. 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.
Bel Youssouf G. Mountessou: Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Tsahnang Fofack Hans Merlin: Laboratoire Optique et Applications, Centre de Physique Atomique Moléculaire et Optique Quantique, Faculté des Sciences, Université de Douala, B.P. 8580, Douala, Cameroon; Analytical, Structural and Materials Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Douala, B.P. 24157, Douala, Cameroon
Pouyewo Ariane: 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; Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Joëlle Nadia Nouping Fekoua: 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; Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Takoua Bella Jean Yves: Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Tchuifon Tchuifon Donald Raoul: 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
Auguste Abouem A Zintchem: Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Gouet Bebga: Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon
Ndassa Ibrahim Mbouombouo: Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon; Department of Applied Chemistry, Faculty of Science, University of Ebolowa, P.O. Box 118, Ebolowa, Cameroon; Corresponding author. Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon.
Ponnadurai Ramasami: Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, 80837, Mauritius; Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, Doornfontein, 2028, South Africa; Corresponding author. Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, 80837, Mauritius.

Journal volume & issue: Vol. 10, no. 9
p. e29560

Abstract

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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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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