In:
Antiviral Chemistry and Chemotherapy, SAGE Publications, Vol. 18, No. 4 ( 2007-08), p. 225-242
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 β-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.
Type of Medium:
Online Resource
ISSN:
2040-2066
,
2040-2066
DOI:
10.1177/095632020701800406
Language:
English
Publisher:
SAGE Publications
Publication Date:
2007
detail.hit.zdb_id:
2130088-4
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