Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors.
Bioorg Med Chem Lett
; 23(1): 62-5, 2013 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-23218713
ABSTRACT
Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and α-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED(50) of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as α-ketoheterocycles and α-ketoesters.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Peptídeo Hidrolases
/
Inibidores de Proteases
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Sulfitos
/
Proteínas Virais
/
Norovirus
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos