Therapy and Prevention of Cytomegalovirus Infections

Skolnik, Paul R.; Hirsch, Martin S.

doi:10.1007/978-1-4613-1715-9_11

Cited by 5 publications

(4 citation statements)

References 199 publications

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“…Effective treatment of post-herpetic neuralgia remains to be found, but longer treatment might give better results in this troublesome form of zoster. Two compounds have shown efficacy in treatment of CMV infections: foscarnet (PFA) and ganciclovir (DHPG) (14,19). Both these compounds show anti-CMV activity in cell cultures, and results in animal models indicate that rat and mouse CMV infection also responds to these drugs (14,19).…”

Section: Herpesvirusesmentioning

confidence: 97%

“…Two compounds have shown efficacy in treatment of CMV infections: foscarnet (PFA) and ganciclovir (DHPG) (14,19). Both these compounds show anti-CMV activity in cell cultures, and results in animal models indicate that rat and mouse CMV infection also responds to these drugs (14,19). Clinical efficacy of foscarnet and ganciclovir has, however, not been seen in all types of CMV infections, and the lack of therapeutic response in bone marrow transplant patients with CMV pneumonitis might be due to pathogenesis involving immune reactions rather than a lytic CMV replication in lung tissue.…”

Section: Herpesvirusesmentioning

confidence: 99%

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Screening for new agents

Öberg

Vrang

1990

Eur. J. Clin. Microbiol. Infect. Dis.

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Screening for new antiviral drugs is concentrated on a search for inhibitors of the human immunodeficiency virus, herpesviruses, influenza virus, hepatitis B virus and rhinovirus. The first step in the process is usually the screening of virus-infected cell cultures followed by secondary screening in infected animals. The relevance of the different screening methods for predicting clinical efficacy is at present uncertain due to the low number of compounds evaluated in double-blind placebo-controlled clinical trials. As a consequence of the con-siderable activity in ongoing research on antiviral drugs the predictive value of the screening systems is expected to improve.

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Section: Herpesvirusesmentioning

confidence: 97%

Section: Herpesvirusesmentioning

confidence: 99%

Screening for new agents

Öberg

Vrang

1990

Eur. J. Clin. Microbiol. Infect. Dis.

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“…Although a number of compounds are active against HCMV in vitro (Colacino and Lopez, 1983;Field et al, 1983;Mar et al, 1984;Plotkin et al, 1985), only the acyclic nucleosides ganciclovir (DHPG) and acyclovir and the pyrophosphate analog foscarnet are sufficiently promising for clinical use against certain HCMV infections (Collaborative DHPG Treatment Study Group, 1986;Jacobson and Mills, 1988;Meyers et al, 1988;Morris, 1988;Rosecan et al, 1986;Shepp et al, 1985;Skolnick and Hirsch, 1988). Nonetheless, these compounds suffer from disadvantages of low potency (Meyers et al, 1988), lack of efficacy in certain circumstances (O'Donnell et al, 1987;Shepp et al, 1985), and cytotoxic manifestations in some therapeutic regimens (Morris, 1988;Skolnik and Hirsch, 1988). Thus, there is yet a substantial need to discover more potent and safer drugs to treat HCMV infections.…”

Section: Introductionmentioning

confidence: 99%

Activity of acyclic halogenated tubercidin analogs against human cytomegalovirus and in uninfected cells

et al. 1991

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Novel acyclic halogenated tubercidins (4-amino-5-halo-7-[(2-hydroxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidines) were examined for their ability to inhibit human cytomegalovirus (HCMV) in yield reduction assays. 5-Bromo acyclic tubercidin (compound 102) was a more potent inhibitor of virus replication than the chloro- and iodo-substituted analogs (compounds 100 and 104). At a 100 microM concentration, the bromo and chloro compounds were more potent than acyclovir but not ganciclovir. Virus titers were reduced more than 99% by compounds 102 and 104 whereas compound 100 and the equally potent acyclovir reduced titers by only 90%. Quantitation of viral DNA by DNA hybridization demonstrated strong inhibition of HCMV DNA synthesis by these compounds. The most potent inhibitor, compound 102, had a 50% inhibitory (I50) concentration (1.6 microM) comparable to that of ganciclovir (1.8 microM). Cytotoxicity in uninfected human cells was evaluated and revealed the following: cell growth rates slowed markedly in the presence of 10 microM compound 102 whereas the same concentration of compounds 100 and 104 led to only a slight prolongation of population doubling time; these compounds inhibited cellular DNA synthesis but not RNA or protein synthesis, as measured by incorporation of radiolabeled precursors into acid-precipitable macromolecules; flow cytometry indicated that compound 102 was a mid-S phase blocker, and adenosine antagonized the inhibition of [3H]dThd incorporation by compound 102. Together, these results demonstrate that compound 102 is a potent and selective inhibitor of viral and cellular DNA synthesis and that acyclic halogenated pyrrolo-pyrimidine nucleosides may have therapeutic potential.

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“…Moreover, HCMV may interact at the molecular level with human immunodeficiency virus and enhance the consequences of human immunodeficiency virus infection (3). Although a number of compounds are active against HCMV in vitro (2, 5, 11), only gancyclovir, acyclovir (ACV), and foscarnet are sufficiently promising for clinical use against certain HCMV infections (8,13,15,16,19).…”

mentioning

confidence: 99%

Antagonism of the cytotoxic but not antiviral effects of ara-sangivamycin by adenosine

Birch

Krawczyk

Townsend

et al. 1989

Antimicrob Agents Chemother

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Inhibition of DNA synthesis by ara-sangivamycin was antagonized by adenosine. The 50% inhibitory concentrations increased 1.6-to 32-fold in the presence of 1.0 to 50 ,uM adenosine, respectively. In contrast, the inhibition of human cytomegalovirus replication by ara-sangivamycin was not antagonized by as much as 50 ,uM adenosine. This suggests that different enzymes were responsible for the phosphorylation of ara-sangivamycin in uninfected and infected cells.

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Therapy and Prevention of Cytomegalovirus Infections

Cited by 5 publications

References 199 publications

Screening for new agents

Screening for new agents

Activity of acyclic halogenated tubercidin analogs against human cytomegalovirus and in uninfected cells

Antagonism of the cytotoxic but not antiviral effects of ara-sangivamycin by adenosine

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