Identification and characterization of nonsubstrate based inhibitors of the essential dengue and West Nile virus proteases.
Bioorg Med Chem
; 13(1): 257-64, 2005 Jan 03.
Article
em En
| MEDLINE
| ID: mdl-15582469
ABSTRACT
The 72 known members of the flavivirus genus include lethal human pathogens such as Yellow Fever, West Nile, and Dengue viruses. There is at present no known chemotherapy for any flavivirus and no effective vaccines for most. A common genomic organization and molecular mechanisms of replication in hosts are shared by flaviviruses with a viral serine protease playing a pivotal role in processing the viral polyprotein into component polypeptides, an obligatory step in viral replication. Using the structure of the dengue serine protease complexed with a protein inhibitor as a template, we have identified five compounds, which inhibit the enzyme. We also describe parallel inhibitory activity of these compounds against the West Nile virus Protease. A few of the compounds appear to provide a template for design of more potent and specific inhibitors of the dengue and West Nile virus proteases. Sequence similarities among flaviviral proteases suggests that such compounds might also possibly inhibit other flaviviral proteases.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
/
Inibidores de Proteases
/
Vírus do Nilo Ocidental
/
Vírus da Dengue
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos