Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

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Authors: Darci R Smith, Monica Ogg, Aura Garrison, et al

Published Date February 2010 Volume 2010:2 Pages 9 - 20

DOI: http://dx.doi.org/10.2147/VAAT.S6903

Darci R Smith¹, Monica Ogg¹, Aura Garrison¹, Abdul Yunus², Anna Honko¹, Josh Johnson¹, Gene Olinger¹, Lisa E Hensley¹, Michael S Kinch

¹United States Army Medical Research Institute of Infectious Diseases (USAMRII D), Fort Detrick, MD, USA; ²Functional Genetics, Inc., Gaithersburg, MD, USA

Abstract: The family Bunyaviridae is a diverse group of negative-strand RNA viruses that infect a wide range of arthropod vectors and animal hosts. Based on the continuing need for new therapeutics to treat bunyavirus infections, we evaluated the potential efficacy of FGI-106, a small-molecular compound that previously demonstrated activity against different RNA viruses. FGI-106 displayed substantial antiviral activity in cell-based assays of different bunyavirus family members, including Asian and South American hantaviruses (Hantaan virus and Andes virus), Crimean-Congo hemorrhagic fever virus, La Crosse virus, and Rift Valley fever virus. The pharmacokinetic profile of FGI-106 revealed sufficient exposure of the drug to critical target organs (lung, liver, kidney, and spleen), which are frequently the sites of bunyavirus replication. Consistent with these findings, FGI-106 treatment delivered via intraperitoneal injection prior to virus exposure was sufficient to delay the onset of Rift Valley fever virus infection in mouse-based models and to enhance survival in the face of an otherwise lethal infection. Altogether, these results suggest a potential opportunity for the use of FGI-106 to treat infections by members of the family Bunyaviridae.

Keywords: Rift Valley fever virus, bunyavirus, hantavirus, antiviral, therapeutic

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