Western Equine Encephalitis virus (WEEV), a member of the genus Alphavirus, causes a range of ailments from fevers to encephalitis with severe neuronal sequelea.  WEEV is weaponizable and poses a potential bioterrorism agent.   Through HTS screening for inhibitors of WEEV RNA replication, CCG-32091 (IC50 = 24 �M) was selected for further SAR development.  The thienopyrrole core in CCG-32091 was replaced with an indole to minimize metabolic instability.  The resulting analog, CCG-102516, has an IC50 = 15 �M.  Further SAR development around CCG-102516 aims to improve potency, minimize toxicity, and enhance physical chemical properties.  Enantiomeric analogs CCG-203926 and CCG-203927 (IC50 = 7.1 �M and >100 �M, respectively) were taken into preliminary animal studies.  Mice were infected with neuroadapted Sindbis virus and treated at 10 mg/kg and 30 mg/kg IP twice a day. CCG-203926, but not CCG-203927, showed improvements in both severity of disease and survival in a dose dependent manner.

Small molecule anti-virals against western equine encephalitis virus

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.