Journal of Antivirals & Antiretrovirals
Open Access

Abstract

A Kinase Inhibitor Cocktail as a Prophylaxis in the Syrian Golden Hamster Pirital Virus Model

Jennifer Garver, Rebecca Gillespie, Marcus Carlton and Eric Vela

Arena viruses are negative strand RNA viruses that have the potential to cause a wide spectrum of disease including hemorrhagic fever in humans and experimental animals. There are currently limited therapeutic treatments available for arena virus infection, which includes ribavirin and in some cases immune plasma. Therapeutic research testing the efficacy of products on arena virus infection can be difficult because work with the arena viruses that cause hemorrhagic fever require Biosafety level (BSL)-4 containment. However, surrogate arena virus animal models have been developed that can be utilized as a screening tool to test product efficacy of antivirals that may have broad acting anti-arena viral activity. Because there is a strong need to develop novel prophylaxis and therapeutics, we have utilized the Syrian golden hamster Pirital virus (PIRV) surrogate model to test antiviral efficacy in a BSL-3 environment. PIRV is a New World arena virus that is not known to cause human disease, but it is capable of causing hemorrhagic fever, morbidity, and complete mortality in the Syrian golden hamster. Thus, we infected hamsters with PIRV and treated with two different dosages of a kinase inhibitor cocktail consisting of genistein and tyrphostin AG1478. Drug efficacy was determined by evaluating physical signs of disease, mortality, viral titers in specific tissues, and terminal viremia. In this study, treating PIRV-infected hamsters with a kinase inhibitor cocktail led to a significant survival rate, lower viral titers, and an absence of viremia in survivors. In all, the results demonstrate the potential of the cocktail as an antiviral against arena virus infection.