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Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.

Abstract
The era of antiviral chemotherapy started more than 50 years with the findings by Domagk and his colleagues that thiosemicarbazones showed activity against vaccinia virus. One of the derivatives, methisazone, was even investigated in the prophylaxis of smallpox. With the successful implementation of the smallpox vaccine, the use of methisazone was not further pursued. Should there be a threat of smallpox or other poxvirus infections, that could not be immediately controlled by vaccination, a therapeutic intervention could be envisaged based on several therapeutic strategies targeted at such cellular enzymes as IMP dehydrogenase, SAH hydrolase, OMP decarboxylase and CTP synthetase, as well as viral enzymes such as the DNA polymerase. Most advanced as a therapeutic or early prophylactic modality to tackle poxvirus infection is cidofovir, which was found active (i) in vitro against all poxviruses studied so far; (ii) in vivo, against vaccinia and cowpox virus infections in experimental animal models; as well as (iii) some human poxvirus infections, such as molluscum contagiosum. In case of an inadvertent poxvirus epidemic, antiviral therapy (i.e. with cidofovir) will offer the possibility to provide short-term prophylaxis, or therapy. Cidofovir should also allow to treat severe complications of vaccination as may happen in for example immunosuppressed patients.
AuthorsJohan Neyts, Erik De Clercq
JournalAntiviral research (Antiviral Res) Vol. 57 Issue 1-2 Pg. 25-33 (Jan 2003) ISSN: 0166-3542 [Print] Netherlands
PMID12615300 (Publication Type: Historical Article, Journal Article, Review)
Chemical References
  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir
Topics
  • Animals
  • Antiviral Agents (therapeutic use)
  • Cidofovir
  • Cytosine (analogs & derivatives, therapeutic use)
  • History, 20th Century
  • Humans
  • Organophosphonates
  • Organophosphorus Compounds (therapeutic use)
  • Poxviridae Infections (drug therapy, history, prevention & control)
  • Smallpox (drug therapy, prevention & control)
  • Time Factors
  • Vaccinia (drug therapy, prevention & control)

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