High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona

Abstract The recent epidemic of Ebola virus disease in West Africa resulted in an unprecedented number of cases and deaths. Due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existin...

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Autores principales:	Anna N. Honko, Joshua C. Johnson, Jonathan S. Marchand, Louis Huzella, Ricky D. Adams, Nicholas Oberlander, Lisa M. Torzewski, Richard S. Bennett, Lisa E. Hensley, Peter B. Jahrling, Gene G. Olinger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3c4b86005dec400d8fd8007eea1d844b
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spelling	oai:doaj.org-article:3c4b86005dec400d8fd8007eea1d844b2021-12-02T12:32:41ZHigh dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona10.1038/s41598-017-06179-y2045-2322https://doaj.org/article/3c4b86005dec400d8fd8007eea1d844b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06179-yhttps://doaj.org/toc/2045-2322Abstract The recent epidemic of Ebola virus disease in West Africa resulted in an unprecedented number of cases and deaths. Due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existing data reporting anti-Ebola activity. Drugs with demonstrated antiviral activity in the nonhuman primate models already approved for another indication or for which there was existing safety data were considered to be priorities for evaluation by the World Health Organization. Sertraline hydrochloride was reported to have anti-Ebola activity in vitro alone and in combination with other approved drugs. Although the efficacy was less than 100% in the murine model, the established safety profile of this product, the potential benefit alone and in combination, as well as the lack of other available options prioritized this compound for testing in the Ebola virus intramuscular rhesus macaque challenge model. Using a blinded dosing strategy, we demonstrated that high dose sertraline monotherapy provided no benefit for the prevention of Ebola virus disease in rhesus macaques with regards to reduction of viral load, morbidity, or survival highlighting the challenges of translating results between in vitro and in vivo models.Anna N. HonkoJoshua C. JohnsonJonathan S. MarchandLouis HuzellaRicky D. AdamsNicholas OberlanderLisa M. TorzewskiRichard S. BennettLisa E. HensleyPeter B. JahrlingGene G. OlingerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna N. Honko Joshua C. Johnson Jonathan S. Marchand Louis Huzella Ricky D. Adams Nicholas Oberlander Lisa M. Torzewski Richard S. Bennett Lisa E. Hensley Peter B. Jahrling Gene G. Olinger High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
description	Abstract The recent epidemic of Ebola virus disease in West Africa resulted in an unprecedented number of cases and deaths. Due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existing data reporting anti-Ebola activity. Drugs with demonstrated antiviral activity in the nonhuman primate models already approved for another indication or for which there was existing safety data were considered to be priorities for evaluation by the World Health Organization. Sertraline hydrochloride was reported to have anti-Ebola activity in vitro alone and in combination with other approved drugs. Although the efficacy was less than 100% in the murine model, the established safety profile of this product, the potential benefit alone and in combination, as well as the lack of other available options prioritized this compound for testing in the Ebola virus intramuscular rhesus macaque challenge model. Using a blinded dosing strategy, we demonstrated that high dose sertraline monotherapy provided no benefit for the prevention of Ebola virus disease in rhesus macaques with regards to reduction of viral load, morbidity, or survival highlighting the challenges of translating results between in vitro and in vivo models.
format	article
author	Anna N. Honko Joshua C. Johnson Jonathan S. Marchand Louis Huzella Ricky D. Adams Nicholas Oberlander Lisa M. Torzewski Richard S. Bennett Lisa E. Hensley Peter B. Jahrling Gene G. Olinger
author_facet	Anna N. Honko Joshua C. Johnson Jonathan S. Marchand Louis Huzella Ricky D. Adams Nicholas Oberlander Lisa M. Torzewski Richard S. Bennett Lisa E. Hensley Peter B. Jahrling Gene G. Olinger
author_sort	Anna N. Honko
title	High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
title_short	High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
title_full	High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
title_fullStr	High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
title_full_unstemmed	High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
title_sort	high dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with ebola virus makona
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3c4b86005dec400d8fd8007eea1d844b
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High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona

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