Inhibition of African swine fever virus DNA synthesis by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine.
The acyclic nucleotide analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] is a potent and selective inhibitor of African swine fever virus (ASFV) replication. Using the DNA-DNA hybridization technique with plasmid pRPEL-2 as probe, we have shown that (S)-HPMPA exerts a specific, dose-dependent, inhibitory effect on viral DNA synthesis. Also, (S)-HPMPA inhibits the production of late viral proteins, especially IP-73, in ASFV-infected MS and Vero cells. When evaluated under the same experimental conditions, phosphonoacetic acid (PAA) also caused an inhibition of viral DNA and late viral protein synthesis but only so at a concentration which was 10- to 20-fold higher than that required for (S)-HPMPA.
Arzuza
O
O
Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
García-Villalón
D
D
Tabarés
E
E
Gil-Fernández
C
C
De Clercq
E
E
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000358:African Swine Fever Virus / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects; D006801:Humans; D007497:Iridoviridae / Q000235:genetics*; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D014709:Vero Cells
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D010746:Phosphonoacetic Acid