title: 2'-C-Methyl branched pyrimidine ribonucleoside analogues: potent inhibitors of RNA virus replication.
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.
authors: Laboratoire Coopératif Idenix-CNRS-Université Montpellier II, Montpellier, France.
authors: Samira
authors: S
authors: Benzaria
authors: Dorothée
authors: D
authors: Bardiot
authors: Tony
authors: T
authors: Bouisset
authors: Clément
authors: C
authors: Counor
authors: Céline
authors: C
authors: Rabeson
authors: Claire
authors: C
authors: Pierra
authors: Richard
authors: R
authors: Storer
authors: Anna Giulia
authors: AG
authors: Loi
authors: Alessandra
authors: A
authors: Cadeddu
authors: Massimo
authors: M
authors: Mura
authors: Chiara
authors: C
authors: Musiu
authors: Michel
authors: M
authors: Liuzzi
authors: Roberta
authors: R
authors: Loddo
authors: Svetlana
authors: S
authors: Bergelson
authors: Vadim
authors: V
authors: Bichko
authors: Edward
authors: E
authors: Bridges
authors: Erika
authors: E
authors: Cretton-Scott
authors: John
authors: J
authors: Mao
authors: Jean-Pierre
authors: JP
authors: Sommadossi
authors: Maria
authors: M
authors: Seifer
authors: David
authors: D
authors: Standring
authors: Michele
authors: M
authors: Tausek
authors: Gilles
authors: G
authors: Gosselin
authors: Paolo
authors: P
authors: La Colla
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects* / Q000502:physiology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides