Details

Autor(en) / Beteiligte

• Zhang, Huaisheng
• Harmon, Moeshia
• Radoshitzky, Sheli R
• Soloveva, Veronica
• Kane, Christopher D
• Duplantier, Allen J
• Ogungbe, Ifedayo Victor

Titel

Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus

Ist Teil von

• ACS medicinal chemistry letters, 2020-11, Vol.11 (11), p.2139-2145

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 nonstructural 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 nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC50 = 2.4 μM (HeLa), 1.6 μM (Vero E6)). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.