Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment

In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated...

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Autores principales:	Michael P. Okoh, Rajeev K. Singla, Chijioke Madu, Opeyemi Soremekun, Johnson Adejoh, Lukman A. Alli, Bairong Shen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	malaria phytomedicine gephyrin metabolite molecular dynamics protease Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/92d69604b2a64890b2d86338d642615a
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spelling	oai:doaj.org-article:92d69604b2a64890b2d86338d642615a2021-12-01T15:21:52ZPhytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment1663-981210.3389/fphar.2021.751032https://doaj.org/article/92d69604b2a64890b2d86338d642615a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.751032/fullhttps://doaj.org/toc/1663-9812In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated for management of malaria by traditional healers. The present study was aimed to cheminformatically analyse the binding potential of artesunate and azadirachtin with various reactive moieties of Gephyrin E, to reduce malaria scourge. With molecular dynamics (MD), binding free energy estimation and binding affinity of artesunate and azadirachtin to Gephyrin E was done. GRIP docking was done to study the interactions of these test ligands with Gephyrin E (6FGC). MD simulation gave insights to structural changes upon binding of artesunate and azadirachtin in the ligand-binding pocket of Gephyrin E. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were calculated. From the estimation, azadirachtin had a total binding energy of −36.97 kcal/mol; artesunate had a binding energy of −35.73 kcal/mol. The GRIP docking results provided a clearer evidence that artesunate has comparatively better binding affinity to Gephyrin E than azadirachtin, and the critical binding sites (in activity order) were cavity 3, 2, 8, and 6 for artesunate while for azadirachtin, it was cavity 6, 3, 8, and 2. The GRIP docking provided detailed interactions at the atomic levels, providing evidence; both compounds have chances to overcome the drug resistance problem, albeit higher for artesunate. Our findings added another piece of evidence that azadirachtin may be effective as an anti-malarial agent. The results herein may provide impetus for more studies into bioactive components of plant origin towards the effective management of malaria disease phenotype.Michael P. OkohMichael P. OkohRajeev K. SinglaChijioke MaduOpeyemi SoremekunOpeyemi SoremekunJohnson AdejohLukman A. AlliBairong ShenFrontiers Media S.A.articlemalariaphytomedicinegephyrinmetabolitemolecular dynamicsproteaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	malaria phytomedicine gephyrin metabolite molecular dynamics protease Therapeutics. Pharmacology RM1-950
spellingShingle	malaria phytomedicine gephyrin metabolite molecular dynamics protease Therapeutics. Pharmacology RM1-950 Michael P. Okoh Michael P. Okoh Rajeev K. Singla Chijioke Madu Opeyemi Soremekun Opeyemi Soremekun Johnson Adejoh Lukman A. Alli Bairong Shen Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
description	In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated for management of malaria by traditional healers. The present study was aimed to cheminformatically analyse the binding potential of artesunate and azadirachtin with various reactive moieties of Gephyrin E, to reduce malaria scourge. With molecular dynamics (MD), binding free energy estimation and binding affinity of artesunate and azadirachtin to Gephyrin E was done. GRIP docking was done to study the interactions of these test ligands with Gephyrin E (6FGC). MD simulation gave insights to structural changes upon binding of artesunate and azadirachtin in the ligand-binding pocket of Gephyrin E. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were calculated. From the estimation, azadirachtin had a total binding energy of −36.97 kcal/mol; artesunate had a binding energy of −35.73 kcal/mol. The GRIP docking results provided a clearer evidence that artesunate has comparatively better binding affinity to Gephyrin E than azadirachtin, and the critical binding sites (in activity order) were cavity 3, 2, 8, and 6 for artesunate while for azadirachtin, it was cavity 6, 3, 8, and 2. The GRIP docking provided detailed interactions at the atomic levels, providing evidence; both compounds have chances to overcome the drug resistance problem, albeit higher for artesunate. Our findings added another piece of evidence that azadirachtin may be effective as an anti-malarial agent. The results herein may provide impetus for more studies into bioactive components of plant origin towards the effective management of malaria disease phenotype.
format	article
author	Michael P. Okoh Michael P. Okoh Rajeev K. Singla Chijioke Madu Opeyemi Soremekun Opeyemi Soremekun Johnson Adejoh Lukman A. Alli Bairong Shen
author_facet	Michael P. Okoh Michael P. Okoh Rajeev K. Singla Chijioke Madu Opeyemi Soremekun Opeyemi Soremekun Johnson Adejoh Lukman A. Alli Bairong Shen
author_sort	Michael P. Okoh
title	Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
title_short	Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
title_full	Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
title_fullStr	Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
title_full_unstemmed	Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment
title_sort	phytomedicine in disease management: in-silico analysis of the binding affinity of artesunate and azadirachtin for malaria treatment
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/92d69604b2a64890b2d86338d642615a
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Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment

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