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Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attract...

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Autores principales: Yadav, Pardeep, El-Kafrawy, Sherif A., El-Day, Mai M., Alghafari, Wejdan T., Faizo, Arwa A., Jha, Saurabh Kumar, Dwivedi, Vivek Dhar, Azhar, Esam I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324244/
https://www.ncbi.nlm.nih.gov/pubmed/35888042
http://dx.doi.org/10.3390/life12070952
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author Yadav, Pardeep
El-Kafrawy, Sherif A.
El-Day, Mai M.
Alghafari, Wejdan T.
Faizo, Arwa A.
Jha, Saurabh Kumar
Dwivedi, Vivek Dhar
Azhar, Esam I.
author_facet Yadav, Pardeep
El-Kafrawy, Sherif A.
El-Day, Mai M.
Alghafari, Wejdan T.
Faizo, Arwa A.
Jha, Saurabh Kumar
Dwivedi, Vivek Dhar
Azhar, Esam I.
author_sort Yadav, Pardeep
collection PubMed
description The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV–RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV–RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV–RdRp. Hence, selected natural compounds are admissible inhibitors of JEV–RdRp protein and can be considered for future antiviral drug development studies.
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spelling pubmed-93242442022-07-27 Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus Yadav, Pardeep El-Kafrawy, Sherif A. El-Day, Mai M. Alghafari, Wejdan T. Faizo, Arwa A. Jha, Saurabh Kumar Dwivedi, Vivek Dhar Azhar, Esam I. Life (Basel) Article The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV–RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV–RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV–RdRp. Hence, selected natural compounds are admissible inhibitors of JEV–RdRp protein and can be considered for future antiviral drug development studies. MDPI 2022-06-24 /pmc/articles/PMC9324244/ /pubmed/35888042 http://dx.doi.org/10.3390/life12070952 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yadav, Pardeep
El-Kafrawy, Sherif A.
El-Day, Mai M.
Alghafari, Wejdan T.
Faizo, Arwa A.
Jha, Saurabh Kumar
Dwivedi, Vivek Dhar
Azhar, Esam I.
Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title_full Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title_fullStr Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title_full_unstemmed Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title_short Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus
title_sort discovery of small molecules from echinacea angustifolia targeting rna-dependent rna polymerase of japanese encephalitis virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324244/
https://www.ncbi.nlm.nih.gov/pubmed/35888042
http://dx.doi.org/10.3390/life12070952
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