Activities of acyclic nucleoside phosphonates against Orf virus in human and ovine cell monolayers and organotypic ovine raft cultures.

Abstract

Orf virus, a member of the Parapoxvirus genus, causes a contagious pustular dermatitis in sheep, goats, and humans. Previous studies have demonstrated the activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; cidofovir; Vistide) against orf virus in cell culture and humans. We have evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several orf virus strains in primary lamb keratinocytes (PLKs) and human embryonic lung (HEL) monolayers. HPMPC, (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6- diaminopurine (HPMPDAP), and (R)-9-[3-hydroxy-2-(phosphonomethoxy)propoxy]-2,4-diaminopyrimidine (HPMPO-DAPy) were three of the most active compounds that were subsequently tested in a virus yield assay with PLK and HEL cells by virus titration and DNA quantification. HPMPC, HPMPDAP, and HPMPO-DAPy were evaluated for their activities against orf virus replication in organotypic epithelial raft cultures from differentiated PLK cells. At the highest concentrations (50 and 20 microg/ml), full protection was provided by the three drugs, while at 5 microg/ml, only HPMPDAP and HPMPC offered partial protection. The activities of the three compounds in the raft culture system were confirmed by quantification of infectious virus and viral DNA. These findings provide a rationale for the use of HPMPC and other ANPs in the treatment of orf (contagious ecthyma) in humans and animals.

• Authors: F Dal Pozzo, G Andrei, A Holy, J Van Den Oord, A Scagliarini, E De Clercq, R Snoeck
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 12 Pg. 4843-52 (Dec 2005) ISSN: 0066-4804 [Print] United States
• PMID: 16304144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nucleosides
• Organophosphonates
• Organophosphorus Compounds
• 9-(3-hydroxy-2-phosphonomethoxypropyl)-2,6-diaminopurine
• Cytosine
• Adenine
• Cidofovir

Topics

• Adenine (analogs & derivatives, chemical synthesis, pharmacology)
• Animals
• Cell Line
• Cell Line, Transformed
• Cidofovir
• Cytosine (analogs & derivatives, chemical synthesis, pharmacology)
• Humans
• Keratinocytes (drug effects, virology)
• Nucleosides (chemical synthesis, pharmacology)
• Orf virus (drug effects, metabolism, physiology)
• Organophosphonates (chemical synthesis, pharmacology)
• Organophosphorus Compounds (chemical synthesis, pharmacology)
• Sheep