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

High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona.
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Honko AN, Johnson JC, Marchand JS, Huzella L, Adams RD, Oberlander N, Torzewski LM, Bennett RS, Hensley LE, Jahrling PB, Olinger GG,


Honko AN, Johnson JC, Marchand JS, Huzella L, Adams RD, Oberlander N, Torzewski LM, Bennett RS, Hensley LE, Jahrling PB, Olinger GG, (click to view)

Honko AN, Johnson JC, Marchand JS, Huzella L, Adams RD, Oberlander N, Torzewski LM, Bennett RS, Hensley LE, Jahrling PB, Olinger GG,

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Scientific reports 2017 07 197(1) 5886 doi 10.1038/s41598-017-06179-y

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.

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