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-phosphono-methoxypropyl)cytosine] (HPMPC, cidofovir, CDV, Vistide®) against Orf virus in cell culture (Nettleton et al., 2000, Antiviral Res., 48: 205-8) and in humans (Geerinck et al., 2001, J. Med. Virol. 64: 543-9). We evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several Orf virus strains in primary lamb keratinocytes (PLK) and human embryonic lung (HEL) monolayers. The activity of the ANPs was higher in HEL than in PLK cells: the EC50 values for HPMPC were in the range of 0.1-0.8 Ìg/ml and 0.2-3.5 Ìg/ml in HEL and PLK, respectively; (S)-9-(3-hydroxy-2-phosphonomethoxy-propyl)-2,6-diaminopurine (HPMPDAP) was active at 0.08 to 0.1 Ìg/ml in HEL and at 0.1 to 3.2 Ìg/ml in PLK. The activity of HPMPC, HPMPDAP and (S)-9-(3-hydroxy-2-(phosphonomethoxy-propoxy)-2,4-diaminopyrimidine (HPMPO-DAPY) was confirmed by virus titration and DNA quantification at different time points in both cell lines. HPMPC, HPMPDAP and HPMPO-DAPY were evaluated for their activity against Orf virus replication in organotypic epithelial raft cultures from differentiated PLK cells. At the highest concentrations (50 and 20 Ìg/ml), a full protection was provided by the three drugs, while at 5 Ìg/ml only HPMPDAP and HPMPC offered partial protection. These findings confirm the activity of HPMPC and other ANPs against Orf virus and provide a rationale for their use in the treatment of orf (contagious ecthyma) in humans and animals.

Activity of Acyclic Nucleoside Phosphonates against Orf virus in vitro and ex vivo.

DAL POZZO, FABIANA;SCAGLIARINI, ALESSANDRA;
2004

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-phosphono-methoxypropyl)cytosine] (HPMPC, cidofovir, CDV, Vistide®) against Orf virus in cell culture (Nettleton et al., 2000, Antiviral Res., 48: 205-8) and in humans (Geerinck et al., 2001, J. Med. Virol. 64: 543-9). We evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several Orf virus strains in primary lamb keratinocytes (PLK) and human embryonic lung (HEL) monolayers. The activity of the ANPs was higher in HEL than in PLK cells: the EC50 values for HPMPC were in the range of 0.1-0.8 Ìg/ml and 0.2-3.5 Ìg/ml in HEL and PLK, respectively; (S)-9-(3-hydroxy-2-phosphonomethoxy-propyl)-2,6-diaminopurine (HPMPDAP) was active at 0.08 to 0.1 Ìg/ml in HEL and at 0.1 to 3.2 Ìg/ml in PLK. The activity of HPMPC, HPMPDAP and (S)-9-(3-hydroxy-2-(phosphonomethoxy-propoxy)-2,4-diaminopyrimidine (HPMPO-DAPY) was confirmed by virus titration and DNA quantification at different time points in both cell lines. HPMPC, HPMPDAP and HPMPO-DAPY were evaluated for their activity against Orf virus replication in organotypic epithelial raft cultures from differentiated PLK cells. At the highest concentrations (50 and 20 Ìg/ml), a full protection was provided by the three drugs, while at 5 Ìg/ml only HPMPDAP and HPMPC offered partial protection. These findings confirm the activity of HPMPC and other ANPs against Orf virus and provide a rationale for their use in the treatment of orf (contagious ecthyma) in humans and animals.
The XVth International Poxvirus and Iridovirus Workshop Keeble College, Oxford September 3rd - 8th, 2004
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144
Dal Pozzo F.; Andrei G. Holy A.; Van Den Oord J.; Scagliarini A.; De Clercq E. and Snoeck R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/17173
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