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Antiviral prophylaxis of smallpox
1Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mbray@niaid.nih.gov
The Journal of Antimicrobial Chemotherapy
|May 28, 2004
Summary
New forms of cidofovir, an antiviral drug, offer promising protection against smallpox. Both inhaled and oral treatments show potential for preventing infection and reducing virus spread, possibly without kidney toxicity.
Area of Science:
- Virology
- Pharmacology
- Infectious Disease Control
Background:
- Current smallpox defenses may be enhanced by antiviral prophylaxis.
- Cidofovir is a long-acting antiviral medication with potential for smallpox treatment.
Purpose of the Study:
- To evaluate aerosolized and orally available cidofovir derivatives for smallpox prophylaxis.
- To assess the efficacy and safety of novel cidofovir formulations against poxviral challenge.
Main Methods:
- Administration of aerosolized cidofovir to mice.
- Development and testing of an orally available cidofovir derivative (alkoxyalkanol ether).
- Assessment of protection against lethal intranasal and aerosol poxviral challenge in mice.
Main Results:
- Aerosolized cidofovir showed prolonged retention in respiratory tissues and protection.
- Orally available cidofovir derivative demonstrated increased antiviral activity and intracellular half-life.
- Oral treatment protected mice against lethal poxviral challenge, suggesting prevention of dissemination.
Conclusions:
- Single aerosol or oral doses of modified cidofovir may offer prolonged protection against smallpox.
- These delivery methods could prevent initial infection and viral spread.
- Potential to avoid nephrotoxicity associated with intravenous cidofovir administration.