Efficacy and Cytotoxicty of Novel Antiviral Compounds against Rift Valley Fever Virus

Rift Valley Fever virus (RVFV) is a ss-RNA virus from the Bunyaviridae family found in Africa and the Arabian Peninsula. The virus is usually transmitted by mosquitoes and predominantly affects livestock; however, humans exposed to bodily fluids or tissue from infected animals can also be infected. In humans, Rift Valley Fever is usually characterized by mild febrile illness; however, in rare cases, the disease becomes more severe and can cause liver disease, encephalitis, vision loss, and hemorrhagic fever. Epizootic RVF can lead to abortion storms in which nearly 100% of pregnancies in infected ruminants result in abortion. RVFV is considered a bioterrorism threat and outbreaks have significant socio-economic impacts. Currently, there are no approved vaccines or therapeutics against RVFV for use in humans. Identification of a safe and effective therapeutic is crucial to public health’s success in the prevention, treatment, and control of Rift Valley Fever. Antiviral properties of compound A3 were identified from a high-throughput screening assay with influenza-A virus. While the mechanism of action of M4 is unknown, A3 is thought to target the enzyme Dihydroorotate Dehydrogenase (DHODH) involved in the de novo pyrimidine biosynthesis pathway. Compound A3 has broad-spectrum antiviral activity and was shown to be effective against both DNA and RNA viruses including, VSV, HCV and HIV-1. To determine efficacy against RVFV, Vero E6 cells were incubated with compounds A3, M4, and Favipiravir (T-705), a known inhibitor of RVFV, at various concentrations with the MP-12 vaccine strain. Amy L. Hartman, Ph.D. EFFICACY AND CYTOTOXICITY OF NOVEL ANTIVIRAL COMPOUNDS AGAINST RIFT VALLEY FEVER VIRUS David Jung, M.P.H. University of Pittsburgh, 2015