pyrazofurin and Virus-Diseases

Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation, chemical properties, biological activities, and structure-activity relationships, with emphasis to selected drugs or drug candidates. Two pyrazole C-nucleoside compounds pyrazofurin (pyrazomycin) and its alpha-epimer pyrazofurin B are active components of potent antivirals approved for therapeutic use in human medicine aimed against various diseases caused by DNA viruses.

Topics: Amides; Antimetabolites; Antiviral Agents; DNA Viruses; Pyrazoles; Ribonucleosides; Ribose; Structure-Activity Relationship; Virus Diseases

The antibiotic pyrazofurin, 3-(beta-D-ribofuranosyl)-4-hydroxypyrazole-5-carboxamide, markedly inhibited the in vitro replication of a number of RNA viruses including Rift Valley fever (RVF), Venezuelan equine encephalomyelitis (VEE), Sandfly, Pichinde, Lassa and LCM virus. Plaque formation was reduced by 80% or more with 2-10 micrograms/ml of pyrazofurin while 2 micrograms/ml reduced by 1000-fold the yield of Lassa and LCM virus in a yield reduction assay. In vivo, pyrazofurin failed to protect mice and guinea pigs against a lethal challenge with VEE and Pichinde virus, respectively. On the other hand, pyrazofurin caused a slight increase in the mean time to death of mice infected with RVF virus.

Topics: Amides; Animals; Antiviral Agents; Arenaviridae; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Encephalitis Virus, Venezuelan Equine; Female; Guinea Pigs; Male; Mice; Phlebovirus; Pyrazoles; Ribavirin; Ribonucleosides; Ribose; Rift Valley fever virus; RNA Viruses; Viral Plaque Assay; Virus Diseases; Yellow fever virus

Topics: Acyclovir; Amantadine; Amides; Antiviral Agents; Guanidine; Guanidines; Guanine; Interferons; Methisazone; Phosphonoacetic Acid; Pyrazoles; Pyrimidines; Ribonucleosides; Ribose; Thymidine; Vidarabine; Virus Diseases