Thursday, February 21, 2013
This week in techniques
Publication and contact
Assays & screens
Cell-free protein synthesis
(CFPS), whole-pathway screen to identify druggable host-virus protein-protein
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.
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;
Contact: Usha F. Lingappa, Prosetta Antiviral Inc., San
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