2'-C-Methyl branched pyrimidine ribonucleoside analogues: potent inhibitors of RNA virus replication
| Autor: | Clément Counor, Michel Liuzzi, Dorothée Bardiot, Massimo Mura, Vadim Bichko, Maria Seifer, Svetlana Bergelson, Richard Storer, Erika Cretton-Scott, Tony Bouisset, John Mao, David Standring, Michele Tausek, Jean-Pierre Sommadossi, Chiara Musiu, Edward G. Bridges, Gilles Gosselin, Roberta Loddo, Alessandra Cadeddu, Paolo La Colla, Anna Giulia Loi, Céline Rabeson, Samira Benzaria, Claire Pierra |
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| Rok vydání: | 2007 |
| Předmět: |
0301 basic medicine
Pyrimidine viruses Hepatitis C virus 030106 microbiology Biology medicine.disease_cause Virus Replication 01 natural sciences Antiviral Agents Virus Cell Line 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Dogs RNA polymerase Cricetinae medicine Animals Humans RNA Viruses chemistry.chemical_classification Molecular Structure RNA RNA virus General Medicine Haplorhini biology.organism_classification Ribonucleoside Pyrimidine Nucleosides Virology 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme chemistry Biochemistry |
| Zdroj: | Antiviral chemistrychemotherapy. 18(4) |
| ISSN: | 0956-3202 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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