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

Darci R. Smith, Monica Ogg, Aura Garrison, Abdul Yunus, Anna Honko, Josh Johnson, Gene Olinger, Lisa E. Hensley, Michael S. Kinch

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9-20
Number of pages12
JournalVirus Adaptation and Treatment
Volume2
Issue number1
StatePublished - 2010
Externally publishedYes

Keywords

  • Antiviral
  • Bunyavirus
  • Hantavirus
  • Rift valley fever virus
  • Therapeutic

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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