Broad-spectrum antiviral activity of carbodine, the carbocyclic analogue of cytidine.
Carbocyclic cytidine (C-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [pox (vaccinia)], (+)RNA viruses [toga (Sindbis, Semliki forest), corona], (-)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), rhabdo (vesicular stomatitis)] and (+/-)RNA viruses (reo). The target enzyme of C-Cyd is supposed to be CTP synthetase that converts UTP to CTP. In keeping with this assumption are the observations that (i) C-Cyd effects a dose-dependent inhibition of RNA synthesis in both virus-infected and uninfected cells, and (ii) exogenous addition of either Urd or Cyd reverses both the antiviral and cytocidal activity of C-Cyd, whereas addition of dThd or dCyd fails to do so. The selectivity of C-Cyd against Sindbis, vesicular stomatitis and reo virus is markedly increased when C-Cyd is combined with Cyd (10 micrograms/mL). This combination may therefore be worth pursuing as a chemotherapeutic modality for the treatment of virus infections.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
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E
De Clercq
R
R
Bernaerts
Y F
YF
Shealy
J A
JA
Montgomery
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003562:Cytidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004267:DNA Viruses / Q000187:drug effects*; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D012328:RNA Viruses / Q000187:drug effects*; D012254:Ribavirin / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014709:Vero Cells / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009705:Nucleosides; D012254:Ribavirin; D003562:Cytidine; D012313:RNA; C033357:carbodine; C034072:carbocyclic 3-deazaadenosine; D004247:DNA; D014372:Tubercidin