Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Abstract Japanese encephalitis (JE) virus is a flavivirus causing encephalitis causing neurological damage. RNA-dependent-RNA-polymerase (RdRp) is responsible for genome replication making it excellent anti-viral target. In this study, the crystal structure of JE RdRp (jRdRp) and bioflavonoids repor...

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Autores principales:	Vivek Dhar Dwivedi, Ankita Singh, Sherif Aly El-Kafraway, Thamir A. Alandijany, Arwa A. Faizo, Leena Hussein Bajrai, Mohammad Amjad Kamal, Esam Ibraheem Azhar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a81dbf1e2c134ceb9ce157679add4cd6
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spelling	oai:doaj.org-article:a81dbf1e2c134ceb9ce157679add4cd62021-12-02T15:15:35ZMechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica10.1038/s41598-021-96917-02045-2322https://doaj.org/article/a81dbf1e2c134ceb9ce157679add4cd62021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96917-0https://doaj.org/toc/2045-2322Abstract Japanese encephalitis (JE) virus is a flavivirus causing encephalitis causing neurological damage. RNA-dependent-RNA-polymerase (RdRp) is responsible for genome replication making it excellent anti-viral target. In this study, the crystal structure of JE RdRp (jRdRp) and bioflavonoids reported in Azadirachta indica were retrieved from specific databases. Structure-based virtual screening was employed using MTiOpenScreen server and top four compounds selected with the most negative docking scores. Conformations were redocked using AutoDock Vina; these complexes showed mechanistic interactions with Arg474, Gly605, Asp668, and Trp800 residues in the active site of jRdRp, i.e., guanosine-5′-triphosphate. Furthermore, 100 ns classical molecular dynamics simulation and binding free energy calculation showed stability of docked bioflavonoids in the active jRdRp pocket and significant contribution of van-der-Waals interactions for docked complex stability during simulation. Therefore, this study predicted the anti-viral activity of Gedunin, Nimbolide, Ohchinin acetate, and Kulactone against jRdRp and can be considered for further antiviral drug development.Vivek Dhar DwivediAnkita SinghSherif Aly El-KafrawayThamir A. AlandijanyArwa A. FaizoLeena Hussein BajraiMohammad Amjad KamalEsam Ibraheem AzharNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vivek Dhar Dwivedi Ankita Singh Sherif Aly El-Kafraway Thamir A. Alandijany Arwa A. Faizo Leena Hussein Bajrai Mohammad Amjad Kamal Esam Ibraheem Azhar Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
description	Abstract Japanese encephalitis (JE) virus is a flavivirus causing encephalitis causing neurological damage. RNA-dependent-RNA-polymerase (RdRp) is responsible for genome replication making it excellent anti-viral target. In this study, the crystal structure of JE RdRp (jRdRp) and bioflavonoids reported in Azadirachta indica were retrieved from specific databases. Structure-based virtual screening was employed using MTiOpenScreen server and top four compounds selected with the most negative docking scores. Conformations were redocked using AutoDock Vina; these complexes showed mechanistic interactions with Arg474, Gly605, Asp668, and Trp800 residues in the active site of jRdRp, i.e., guanosine-5′-triphosphate. Furthermore, 100 ns classical molecular dynamics simulation and binding free energy calculation showed stability of docked bioflavonoids in the active jRdRp pocket and significant contribution of van-der-Waals interactions for docked complex stability during simulation. Therefore, this study predicted the anti-viral activity of Gedunin, Nimbolide, Ohchinin acetate, and Kulactone against jRdRp and can be considered for further antiviral drug development.
format	article
author	Vivek Dhar Dwivedi Ankita Singh Sherif Aly El-Kafraway Thamir A. Alandijany Arwa A. Faizo Leena Hussein Bajrai Mohammad Amjad Kamal Esam Ibraheem Azhar
author_facet	Vivek Dhar Dwivedi Ankita Singh Sherif Aly El-Kafraway Thamir A. Alandijany Arwa A. Faizo Leena Hussein Bajrai Mohammad Amjad Kamal Esam Ibraheem Azhar
author_sort	Vivek Dhar Dwivedi
title	Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
title_short	Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
title_full	Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
title_fullStr	Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
title_full_unstemmed	Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica
title_sort	mechanistic insights into the japanese encephalitis virus rna dependent rna polymerase protein inhibition by bioflavonoids from azadirachta indica
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a81dbf1e2c134ceb9ce157679add4cd6
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Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

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