The present invention from UW Madison inventors and collaborators is a set of two distinct small molecule scaffolds that have been developed as antiviral agents against Venezuelan Equine Encephalitic Virus (VEEV). One of the scaffolds was used previously while the inventor was at Kansas:
The second scaffold is newly designed variation on the Kansas scaffold:
The compounds were optimized using a traditional medicinal chemistry platform, guided by a VEEV CPE assay, cellular toxicity assay, viral titer reduction assay, ADME assessment, pharmacokinetic data in mice, and efficacy data in mice. The best compounds from both classes show low nanomolar potency in cells against VEEV and WEEV without any incidence of cytotoxicity.