Effect of Phosphonoacetate on Marek's Disease Virus Replication

Lee, Lucy F.; Nazerian, K.; Leinbach, Susan S.; Reno, John M.; Boezi, John A.

doi:10.1093/jnci/56.4.823

Cited by 45 publications

(23 citation statements)

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“…Higher-molecular-weight esters, such as n-octyl and t-butyl [8,9] were less active. Benzyl [10], cyclohexyl [11], and 2-adamantyl [12] esters were much less active.…”

Section: Methodsmentioning

confidence: 91%

“…Phosphonoacetic acid (PAA) has been previously shown to suppress replication of herpes simplex virus (1,19), avian herpesvirus (11), cytomegalovirus (9), Epstein-Barr virus (16,23,27), vaccinia virus, equine abortion virus, and varicella-zoster virus (1,18) in tissue culture. Promising results in the treatment of ocular, cutaneous, and encephalitic herpesvirus infections in mice, hamsters, and rabbits have been documented (4,5,14,17,21,25).…”

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confidence: 99%

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Structure-activity studies on phosphonoacetate

Mao¹,

Otis²,

Esch³

et al. 1985

Antimicrob Agents Chemother

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Phosphonoacetic acid is a selective antiherpesvirus agent. More than 100 congeners of phosphonoacetic acid were evaluated in vitro and in vivo to understand structure-activity relationships in the hope of designing a superior analog. Results showed that the antiherpesvirus activity had highly specific structural requirements. Neither the carboxylic nor the phosphono groups could be replaced. The distance between these two groups is important. Increase of this distance caused complete loss of activity. However, if this distance was maintained, the addition of groups to the methylene carbon resulted in a reduction, but not loss, of activity. On the other hand, decrease of the carbon chain to formic acid did not deteriorate its antiherpes activity. All analogs tested had lower activity than the parent compound. However, some compounds with decreased activity in vitro appeared to have favorable pharmacological properties in vivo.

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“…Higher-molecular-weight esters, such as n-octyl and t-butyl [8,9] were less active. Benzyl [10], cyclohexyl [11], and 2-adamantyl [12] esters were much less active.…”

Section: Methodsmentioning

confidence: 91%

mentioning

confidence: 99%

Structure-activity studies on phosphonoacetate

Mao¹,

Otis²,

Esch³

et al. 1985

Antimicrob Agents Chemother

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“…It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase.Phosphonoacetate is an effective inhibitor of the replication of herpesviruses (11,13,23,25). The inhibition of herpesvirus replication is through an effect on the viral-induced deoxyribonucleic acid (DNA) polymerase (9,(14)(15)(16)18).…”

mentioning

confidence: 99%

“…These compounds are also of interest at the enzymological level for the information that they might provide about the binding site on the herpesvirus-induced DNA polymerase. Consequently, using as an assay procedure the ability to inhibit the herpesvirus-induced DNA polymerase or the ability to block herpesvirus replication in cell culture or in animals, many other phosphonates have been looked at (10,13,14,23 with NaOH, and the product was recrystallized several times from water to give trisodium phosphonoformate hexahydrate. Phosphorus analysis (1) for CNa3O5P .6H20 gave a molecular weight of 299 (in theory, 300).…”

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confidence: 99%

Inhibition of Herpesvirus Replication and Herpesvirus-Induced Deoxyribonucleic Acid Polymerase by Phosphonoformate

Reno

Lee

Boezi

1978

Antimicrob Agents Chemother

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100

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Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 ,uM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes simplex virus. It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase.Phosphonoacetate is an effective inhibitor of the replication of herpesviruses (11,13,23,25). The inhibition of herpesvirus replication is through an effect on the viral-induced deoxyribonucleic acid (DNA) polymerase (9,(14)(15)(16)18). In animal model studies, the efficacy of phosphonoacetate as an antiherpesvirus drug has been clearly demonstrated (7,8,12). Its clinical use, however, may be limited because it is somewhat toxic to test animals and because it is accumulated in bone (4).Other phosphonate compounds are of interest as inhibitors of herpesvirus replication because they might exhibit an improved therapeutic ratio over phosphonoacetate either by being more effective inhibitors of virus replication or by being less toxic to animals. These compounds are also of interest at the enzymological level for the information that they might provide about the binding site on the herpesvirus-induced DNA polymerase. Consequently, using as an assay procedure the ability to inhibit the herpesvirus-induced DNA polymerase or the ability to block herpesvirus replication in cell culture or in animals, many other phosphonates have been looked at (10,13,14,23

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“…In vivo studies in the target species (see Table 1A) have been disappointing with phosphonoacetic acid (PAA) and MDV (Lee et al, 1976) and Phosphonoformic acid (PFA) and PHV (Vindevogel et aI., 1982). No positive effect was demonstrated in Marek's disease-infected chicks treated for 28 days at 500mg PAA kg-1 day" i.p, or in pigeon herpesvirus-infected pigeons and budgerigars treated for 10 days at 1OOmg PFA kg-1 day" i.rn, PHV infection also proved refractory to acyclovir treatment [100mg kg-1 day-1, i.rn., thrice daily] (Thiry et al, 1983) and MDV infection was not ameliorated by the interferon inducer, Poly I:C (Nemes et aI., 1969).…”

Section: Avian Herpesvirusesmentioning

confidence: 99%

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 2. Avian, Piscine, Canine, Porcine, Bovine and Equine Virus Diseases

Rollinson¹

1992

Antivir Chem Chemother

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SummaryThis paper, which is published in two parts, reviews the literature pertaining to antiviral chemotherapy of viruses of veterinary importance. While early reports in the 1970s referred to the chemotherapy of a number of different RNA and DNA viruses, there' was considerable focus in the 1980s, initially on herpesviruses and latterly on retroviruses, and particularly in cats. Details are given of the successful treatments of FeLV and FIV, which have been used as animal models for HIV therapy. 'Therapy of equine, canine, bovine, porcine, avian, and fish diseases is also considered. The high costs of developing and registering a new chemical entity, especially for food species in which extensive toxicity/residue data are required, is the main reason why specific antiviral compounds are not currently available for veterinary use, although some non-specific immune modulators are now emerging. Concurrent availability of appropriate diagnostic tools is a prerequisite for successful veterinary antiviral chemotherapy, as is a greater understanding of the pathogenesis of virus infections in animals and the development of more sophisticated means of drug delivery, appropriate to both food animal species and companion animals (dogs, cats, and horses). Additionally, antiviral agents are valuable as research tools per se, as opposed to solely as chemotherapeutic agents. Part 1 covers the feline virus diseases, while part 2 includes the other viruses~f veterinary importance, in dogs, horses, cattle, pigs, birds, and fish.

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Effect of Phosphonoacetate on Marek's Disease Virus Replication

Cited by 45 publications

References 0 publications

Structure-activity studies on phosphonoacetate

Structure-activity studies on phosphonoacetate

Inhibition of Herpesvirus Replication and Herpesvirus-Induced Deoxyribonucleic Acid Polymerase by Phosphonoformate

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 2. Avian, Piscine, Canine, Porcine, Bovine and Equine Virus Diseases

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