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Assays & screens

Cell-free protein synthesis (CFPS), whole-pathway screen to identify druggable host-virus protein-protein interactions

A CFPS, whole-pathway screen could help identify druggable host-virus protein-protein interactions. The system, which includes three rabies virus proteins involved in virus capsid assembly as well as host cell extract, was used to screen for small molecules that blocked capsid assembly. In a rabies-infected mammalian cell culture model, an optimized lead molecule had an EC50 value of 15-30 nM and a 50% cytotoxicity concentration (CC50) value of about 2.5-10 mM. Next steps are testing hits in animal models of rabies infection, and ongoing work includes using the screen to identify compounds that inhibit other viral infections.

SciBX 6(7); doi:10.1038/scibx.2013.173
Published online Feb. 21, 2013

Patent applications filed for the small molecules and the screening strategy; Prosetta Antiviral Inc. has partnered with Bristol-Myers Squibb Co. to use the screening strategy to develop molecules for HIV and has ongoing discussions for partnering with two undisclosed pharmas for other indications

Lingappa, U.F. et al. Proc. Natl. Acad. Sci. USA; published online Feb. 12, 2013;
doi:10.1073/pnas.1210198110
Contact: Usha F. Lingappa, Prosetta Antiviral Inc., San Francisco, Calif.
e-mail:
vlingappa@prosetta.com