Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV’s non-structural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent non-peptidic covalent inhibitors of nsP2 cysteine protease represented by compound <b>11</b> (VEEV TrD, EC<sub>50</sub> = 2.4 mM (HeLa), 1.6 mM (Vero E6). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.

Vinyl sulfone-based inhibitors of non-structural protein 2 block the replication of Venezuelan equine encephalitis virus

ACS Spring Meeting 2021

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