Evolution of Therapy for Cytomegalovirus Infection

Verheyden, Julien P. H.

doi:10.1093/clinids/10.supplement_3.s477

Cited by 37 publications

(18 citation statements)

References 85 publications

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“…Furthermore, human cytomegalovirus infections can produce serious congenital defects in newborns (Stagno et aI., 1982;Britt et aI., 1991). Ganciclovir [9-(1 ,3-dihydroxy-2-propoxymethyl)guanine, DHPGj and Foscavir [foscarnet, phosphonoformic acid (PFA)l are currently the only drugs for the treatment of severe CMV infections (Verheyden, 1988;Emanuel, 1990). Our laboratory recently reported the potent and selective anti-CMV activity of the acyclic nucleoside phosphonate, HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosinej (Snoeck et aI., 1988;Neyts et al, 1990Neyts et al, , 1991aNeyts et al, ,b, 1992a.…”

Section: Introductionmentioning

confidence: 99%

Poly(Hydroxy)Carboxylates as Selective Inhibitors of Cytomegalovirus and Herpes Simplex Virus Replication

Neyts

Snoeck

Wutzler

et al. 1992

Antivir Chem Chemother

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SummaryPolyhydroxycarboxylates (MW 3800-14000) derived from phenolic (PDP) compounds were found to be selective inhibitors of human cytomegalovirus (CMV), herpes simplex Virus type 1 (HSV-1), type 2 (HSV-2), thymidine kinase-deficient (TK-c) HSV-1 and vaccinia virus replication at concentrations that are not toxic to the host cells. The PDP compounds were not inhibitory to parainfluenza virus, reovirus, Sindbis virus, or Semliki forest virus. The polycarboxylate aurintricarboxylic acid (ATA) (MW 1149-3336) also proved inhibitory to CMV and HSV replication. The anti-CMV and anti-HSV activities of the ATA polymers increased with increasing molecular weight. The mechanism of anti-CMV activity of both the PDP and ATA series of compounds can be attributed to the inhibition of virion attachment to the cells, probably due to an interaction of these polyanionic compounds with the positively charged domains of the viral envelope glycoproteins.

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Section: Introductionmentioning

confidence: 99%

Poly(Hydroxy)Carboxylates as Selective Inhibitors of Cytomegalovirus and Herpes Simplex Virus Replication

Neyts

Snoeck

Wutzler

et al. 1992

Antivir Chem Chemother

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“…The initial step yields ganciclovir monophosphate: this step is rate-limiting and is catalyzed by the thymidine kinases derived from herpes viruses. GCV therefore exhibits broad-spectrum activity against a variety of DNA viruses such as herpes simplex virus, human cytomegalovirus, varicella-zoster virus, Epstein-Barr virus, human herpes virus-6 and various animal cytomegaloviruses [3][4][5]. Subsequent further phosphorylation is catalyzed by cellular kinases.…”

Section: Introductionmentioning

confidence: 99%

Ganciclovir nucleotides accumulate in mitochondria of rat liver cells expressing the herpes simplex virus thymidine kinase gene

Geutskens

Kuilenburg

et al. 2003

The Journal of Gene Medicine

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“…HCMV also leads to severe clinical manifestations in the foetus or neonate (Stagno et al, 1982;Britt et al, 1991). Currently, only ganciclovir and foscarnet are used for the treatment of severe HCMV infections (Verheyden, 1988;Emanuel, 1990). However, both compounds may result in serious sideeffects (i.e.…”

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confidence: 99%

Protective activity of the lipid A analogue GLA-60 against murine cytomegalovirus infection in immunodeficient mice

Ikeda

Neyts²,

Matsuura³

et al. 1993

Journal of General Virology

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The immunomodulating and murine cytomegalovirus (MCMV)-inhibiting effects of the synthetic lipid A subunit analogue GLA-60 were investigated in different strains of immunodeficient mice. Peritoneal natural killer (NK) cells obtained from nude (nu/nu) C57BL/6 mice or normal NMRI mice, which had been treated intraperitoneaUy with 10 gg of GLA-60 1 day earlier, exhibited a greater cytolytic activity than those from untreated mice. GLA-60 also stimulated NK cell activity in SCID (severe combined immune deficiency) mice (which are T and B cell-defective), but not in NK celldefective beige (C57BL/6 bg/bg) mice. GLA-60 also enhanced the phagocytic activity of peritoneal macrophages in beige, nude and NMRI mice, but not in SCID mice. GLA-60, when administered as a single 150 gg dose 1 day before infection, completely protected beige mice against MCMV-associated mortality. It also caused a significant increase in the life-span of MCMV-infected nude and SCID mice.

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Evolution of Therapy for Cytomegalovirus Infection

Cited by 37 publications

References 85 publications

Poly(Hydroxy)Carboxylates as Selective Inhibitors of Cytomegalovirus and Herpes Simplex Virus Replication

Poly(Hydroxy)Carboxylates as Selective Inhibitors of Cytomegalovirus and Herpes Simplex Virus Replication

Ganciclovir nucleotides accumulate in mitochondria of rat liver cells expressing the herpes simplex virus thymidine kinase gene

Protective activity of the lipid A analogue GLA-60 against murine cytomegalovirus infection in immunodeficient mice

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