Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study

Foot-and-mouth disease (FMD) vaccine does not afford early effective protection until adaptive immune protection caused by the vaccination occurs. Therefore, an alternative prophylactic application of antiviral agents for inhibition of the FMD virus is needed, and this is the scope of this study. In...

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Autores principales:	Mohammed M. S. Wassel, Wael M. Gamal El-Din, Ahmed Ragab, Gameel A. M. Elhag Ali, Yousry A. Ammar
Formato:	article
Lenguaje:	EN
Publicado:	Egyptian Society for Animal Management 2020
Materias:	adamantane derivatives amantadine antiviral bhk-21 cells fmdv Zoology QL1-991 Veterinary medicine SF600-1100 Animal biochemistry QP501-801
Acceso en línea:	https://dx.doi.org/10.21608/javs.2020.118001 https://doaj.org/article/77e9ec5ab95e45c6961598879de0e644
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spelling	oai:doaj.org-article:77e9ec5ab95e45c6961598879de0e6442021-12-02T17:04:17ZAntiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Studyhttps://dx.doi.org/10.21608/javs.2020.1180011687-40722090-3308https://doaj.org/article/77e9ec5ab95e45c6961598879de0e6442020-10-01T00:00:00Zhttps://javs.journals.ekb.eg/article_118001.htmlhttps://doaj.org/toc/1687-4072https://doaj.org/toc/2090-3308Foot-and-mouth disease (FMD) vaccine does not afford early effective protection until adaptive immune protection caused by the vaccination occurs. Therefore, an alternative prophylactic application of antiviral agents for inhibition of the FMD virus is needed, and this is the scope of this study. In this study, we tested nine adamantane-pyrazole derivatives that could exhibit antiviral activity against FMDV infection either in vitro through baby hamster kidney cells (BHK-21 cells) infected with FMD virus serotypes O pan Asia. Cytotoxicity Concentration 50 (CC50) activity of pyrazole derivatives (1, 2, 3, 4, 5a,b, 6a-c) were detected on BHK-21 cells and ranged between 500 to 3000µg/ml. Inhibitory Concentration 50 (IC50) on BHK-21 was achieved only for the most promising three derivatives 6a-c and exhibited an antiviral activity with a therapeutic index of 30, and that was reflected on the antiviral activity response in baby mice with different concentrations where a concentration of 50 µg/ml for pyrazole derivatives 6a and 6c compounds and 40 µg/ml for bis-tolyl pyrazole 6b that achieve 100% protection and this results was as effective as 50 µg/ml of amantadine. Specifically, diaryl pyrazole derivatives 6a-c that protected for six days following FMDV challenge. These results suggested that pyrazole derivatives 6a-c could be used as an effective antiviral agent against FMD virus infection. Molecular docking simulation of the target compounds 6a-c had good binding energy and the tested compounds recommended being an excellent 3C protease inhibitor compared to Amantadine and Ribavirin. These ﬁndings may explain the antiviral activity of the target compounds.Mohammed M. S. WasselWael M. Gamal El-Din Ahmed RagabGameel A. M. Elhag AliYousry A. AmmarEgyptian Society for Animal Managementarticleadamantane derivativesamantadineantiviralbhk-21 cellsfmdvZoologyQL1-991Veterinary medicineSF600-1100Animal biochemistryQP501-801ENJournal of Applied Veterinary Sciences, Vol 5, Iss 4, Pp 37-46 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	adamantane derivatives amantadine antiviral bhk-21 cells fmdv Zoology QL1-991 Veterinary medicine SF600-1100 Animal biochemistry QP501-801
spellingShingle	adamantane derivatives amantadine antiviral bhk-21 cells fmdv Zoology QL1-991 Veterinary medicine SF600-1100 Animal biochemistry QP501-801 Mohammed M. S. Wassel Wael M. Gamal El-Din Ahmed Ragab Gameel A. M. Elhag Ali Yousry A. Ammar Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
description	Foot-and-mouth disease (FMD) vaccine does not afford early effective protection until adaptive immune protection caused by the vaccination occurs. Therefore, an alternative prophylactic application of antiviral agents for inhibition of the FMD virus is needed, and this is the scope of this study. In this study, we tested nine adamantane-pyrazole derivatives that could exhibit antiviral activity against FMDV infection either in vitro through baby hamster kidney cells (BHK-21 cells) infected with FMD virus serotypes O pan Asia. Cytotoxicity Concentration 50 (CC50) activity of pyrazole derivatives (1, 2, 3, 4, 5a,b, 6a-c) were detected on BHK-21 cells and ranged between 500 to 3000µg/ml. Inhibitory Concentration 50 (IC50) on BHK-21 was achieved only for the most promising three derivatives 6a-c and exhibited an antiviral activity with a therapeutic index of 30, and that was reflected on the antiviral activity response in baby mice with different concentrations where a concentration of 50 µg/ml for pyrazole derivatives 6a and 6c compounds and 40 µg/ml for bis-tolyl pyrazole 6b that achieve 100% protection and this results was as effective as 50 µg/ml of amantadine. Specifically, diaryl pyrazole derivatives 6a-c that protected for six days following FMDV challenge. These results suggested that pyrazole derivatives 6a-c could be used as an effective antiviral agent against FMD virus infection. Molecular docking simulation of the target compounds 6a-c had good binding energy and the tested compounds recommended being an excellent 3C protease inhibitor compared to Amantadine and Ribavirin. These ﬁndings may explain the antiviral activity of the target compounds.
format	article
author	Mohammed M. S. Wassel Wael M. Gamal El-Din Ahmed Ragab Gameel A. M. Elhag Ali Yousry A. Ammar
author_facet	Mohammed M. S. Wassel Wael M. Gamal El-Din Ahmed Ragab Gameel A. M. Elhag Ali Yousry A. Ammar
author_sort	Mohammed M. S. Wassel
title	Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
title_short	Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
title_full	Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
title_fullStr	Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
title_full_unstemmed	Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study
title_sort	antiviral activity of adamantane-pyrazole derivatives against foot and mouth disease virus infection in vivo and in vitro with molecular docking study
publisher	Egyptian Society for Animal Management
publishDate	2020
url	https://dx.doi.org/10.21608/javs.2020.118001 https://doaj.org/article/77e9ec5ab95e45c6961598879de0e644
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Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study

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