ST-148 a potent inhibitor of all four serotypes of DENV in vitro.
We saw this in pre-publication, but it is now out. The number of authors hints they believe it’s an important paper. Looking good, albeit early work. But note, there is nothing here barring them from having more, but holding back more advanced stuff.
A Novel Inhibitor of Dengue Virus Replication That Targets the Capsid Protein
Chelsea M. Byrda, Dongcheng Daia, Douglas W. Grosenbacha, Aklile Berhanua, Kevin F. Jonesa, Kara B. Cardwella, Christine Schneidera, Kristin A. Wineingera, Jessica M. Pagea, Chris Harvera, Eric Stavalea, Shanthakumar Tyavanagimatta, Melialani A. Stonea, Ralf Bartenschlagerb, Pietro Scaturrob, Dennis E. Hrubya and Robert Jordana
Antimicrob. Agents Chemother. January 2013 vol. 57 no. 1 15-25
SIGA Technologies, Inc., Corvallis, Oregon, USA
Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany
Dengue viruses (DENV) infect 50 to 100 million people worldwide per year, of which 500,000 develop severe life-threatening disease. This mosquito-borne illness is endemic in most tropical and subtropical countries and has spread significantly over the last decade. While there are several promising vaccine candidates in clinical trials, there are currently no approved vaccines or therapeutics available for treatment of dengue infection. Here, we describe a novel small-molecule compound, ST-148, that is a potent inhibitor of all four serotypes of DENV in vitro. ST-148 significantly reduced viremia and viral load in vital organs and tended to lower cytokine levels in the plasma in a nonlethal model of DENV infection in AG129 mice. Compound resistance mapped to the DENV capsid (C) gene, and a direct interaction of ST-148 with C protein is suggested by alterations of the intrinsic fluorescence of the protein in the presence of compound. Thus, ST-148 appears to interact with the DENV C protein and inhibits a distinct step(s) of the viral replication cycle.
Received 11 July 2012
Returned for modification 3 August 2012
Accepted 26 September 2012
Published ahead of print 15 October 2012