The goal of the program described here is to develop an antiviral drug for treating and preventing Lassa fever and other hemorrhagic fevers of arenavirus origin. Previous library screening identified several good candidate small molecule inhibitors of Lassa virus entry. Subsequent in vitro and in vivo characterization identified a potent series, ST-193, with broad- spectrum activity against 5 distinct Category A hemorrhagic fever Arenaviruses. This series has shown protective efficacy in two animal models of Lassa fever, guinea pigs and cynomolgus monkeys. The specific objective of this application is to optimize this chemical series to identify an appropriate candidate for preclinical development and to collect the necessary data to support the submission of an application for an Investigational New Drug (IND).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI093387-05
Application #
8897241
Study Section
Special Emphasis Panel (ZAI1-LG-M (J2))
Program Officer
Dempsey, Walla L
Project Start
2011-08-17
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
5
Fiscal Year
2015
Total Cost
$1,296,933
Indirect Cost
$517,094
Name
Kineta, Inc.
Department
Type
DUNS #
809832558
City
Seattle
State
WA
Country
United States
Zip Code
98109
York, Joanne; Nunberg, Jack H (2018) A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity. Methods Mol Biol 1604:157-167
Dai, Dongcheng; Burgeson, James R; Gharaibeh, Dima N et al. (2013) Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole. Bioorg Med Chem Lett 23:744-9
Burgeson, James R; Moore, Amy L; Gharaibeh, Dima N et al. (2013) Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles. Bioorg Med Chem Lett 23:750-6
Burgeson, James R; Gharaibeh, Dima N; Moore, Amy L et al. (2013) Lead optimization of an acylhydrazone scaffold possessing antiviral activity against Lassa virus. Bioorg Med Chem Lett 23:5840-3