2'-C-Methyl branched pyrimidine ribonucleoside analogues: potent inhibitors of RNA virus replication.
Antivir Chem Chemother
; 18(4): 225-42, 2007.
Article
en En
| MEDLINE
| ID: mdl-17907380
ABSTRACT
RNA viruses are the agents of numerous widespread and often severe diseases. Their unique RNA-dependent RNA polymerase (RDRP) is essential for replication and, thus, constitutes a valid target for the development of selective chemotherapeutic agents. In this regard, we have investigated sugar-modified ribonucleoside analogues as potential inhibitors of the RDRP. Title compounds retain 'natural' pyrimidine bases, but possess a beta-methyl substituent at the 2'-position of the D- or L-ribose moiety. Evaluation against a broad range of RNA viruses, either single-stranded positive (ssRNA+), single-stranded negative (ssRNA-) or double-stranded (dsRNA), revealed potent activities for D-2'-C-methyl-cytidine and -uridine against ssRNA+, and dsRNA viruses. None of the L-enantiomers were active. Moreover, the 5'-triphosphates of the active D-enantiomers were found to inhibit the bovine virus diarrhoea virus polymerase. Thus, the 2'-methyl branching of natural pyrimidine ribonucleosides transforms physiological molecules into potent, broad-spectrum antiviral agents that merit further development.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Nucleósidos de Pirimidina
/
Virus ARN
/
Replicación Viral
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Antivir Chem Chemother
Asunto de la revista:
QUIMICA
/
TERAPIA POR MEDICAMENTOS
/
VIROLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia