Structure-activity relationships in the development of allosteric hepatitis C virus RNA-dependent RNA polymerase inhibitors: ten years of research.
Med Res Rev
; 33(5): 934-84, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-22893620
ABSTRACT
Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) possesses a single positive strand RNA genome encoding a polyprotein composed of approximatively 3000 amino acids. The polyprotein is cleaved at multiple sites by cellular and viral proteases to liberate structural and nonstructural (NS) proteins. NS5B, the RNA-dependent RNA polymerase (RdRp), which catalyzes the HCV RNA replication has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). In the last 10 years, a growing number of non-nucleoside compounds have been reported as RdRp inhibitors and few are undergoing clinical trials. Over the past 5 years, several reviews were published all describing potentially active molecules. To the best of our knowledge, only one review covers the structure-activity relationships.(1) In this review, we will discuss the reported non-nucleoside molecules acting as RdRp inhibitors according to their chemical class especially focusing on structure-activity relationship aspects among each class of compounds. Thereafter, we will attempt to address the global structural requirements needed for the design of specific inhibitors of RdRp.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Polimerase Dependente de RNA
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Hepacivirus
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Inibidores Enzimáticos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Med Res Rev
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França