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 #
1R01AI093387-01
Application #
8076702
Study Section
Special Emphasis Panel (ZAI1-LG-M (J2))
Program Officer
Tseng, Christopher K
Project Start
2011-08-17
Project End
2016-07-31
Budget Start
2011-08-17
Budget End
2012-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$1,779,213
Indirect Cost
Name
Siga Technologies, Inc.
Department
Type
DUNS #
932651516
City
Corvallis
State
OR
Country
United States
Zip Code
97333
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