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Infectious disease


HCV NS4B protein; HCV NS5B polymerase

In vitro and in vivo studies identified NS4B-binding compounds that could help treat HCV infection. In a chimeric, humanized mouse model for HCV infection, a phosphate prodrug of an imidazopyridine that bound NS4B decreased viral load with higher potency than a positive control NS5B inhibitor. In various animal models, a modified version of the imidazopyridine showed low-to-moderate clearance, high bioavailability and high plasma drug exposure, which could eliminate the need to use a prodrug. Next steps could include testing the new compound in animal models of HCV infection.
Eiger Biopharmaceuticals Inc.'s NS4B inhibitor clemizole hydrochloride is in Phase I testing to treat HCV infection.
Inovio Pharmaceuticals Inc.'s INO-8000, a synthetic, multiantigen DNA vaccine that targets NS4B and the HCV NS3/4A protease complex, is in preclinical development.

SciBX 6(15); doi:10.1038/scibx.2013.364
Published online April 18, 2013

Patent and licensing status unavailable

Miller, J.F. et al. J. Med. Chem.; published online April 1, 2013;
Contact: Andrew J. Peat, GlaxoSmithKline Research & Development,
Research Triangle Park, N.C.