Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus.
ACS Med Chem Lett
; 11(11): 2139-2145, 2020 Nov 12.
Article
in En
| MEDLINE
| ID: mdl-33214821
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Country/Region as subject:
America do sul
/
Venezuela
Language:
En
Journal:
ACS Med Chem Lett
Year:
2020
Document type:
Article
Affiliation country:
United States