Cutaneous infections of mice with vaccinia or cowpox viruses and efficacy of cidofovir

Quenelle, Debra C.; Collins, Deborah; Kern, Earl R.

doi:10.1016/j.antiviral.2004.02.003

Cited by 36 publications

(29 citation statements)

References 25 publications

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“…Without the use of cyclophosphamide to induce immunosuppression, normal mice treated with cidofovir develop small, nonprogressive lesions and the animals do not die from the infection [8,9]. Athymic nude mice have also been used for studying antiviral treatments of vaccinia virus infection [9,10]. In that model the lesions are not quite as severe as with cyclophosphamide immunosuppression, but treated animals die anyway from the infection.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment with cidofovir, either topically or parenterally, can reduce primary and satellite lesions and delay the time to death. Without the use of cyclophosphamide to induce immunosuppression, normal mice treated with cidofovir develop small, nonprogressive lesions and the animals do not die from the infection [8,9]. Athymic nude mice have also been used for studying antiviral treatments of vaccinia virus infection [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Topical Treatment of Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice with Selected Antiviral Substances

Smee

Bailey

Wong

et al. 2011

Antivir Chem Chemother

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Background: Certain nucleoside, nucleotide and pyrophosphate analogues may be useful for treating severe complications arising as a result of virus dissemination following smallpox (live vaccinia virus) vaccinations, especially in immunocompromised individuals. We used an immunosuppressed hairless mouse model to study the effects of 10 antiviral agents on progressive vaccinia infections. Methods: Hairless mice were immunosuppressed by treatment with cyclophosphamide (100 mg/kg) every 4 days starting 1 day prior to vaccinia virus (WR strain) infection of wounded skin. Topical treatments with antiviral agents were applied twice a day for 7 days starting 5 days after virus exposure. Results: Topical 1% cidofovir cream treatment was effective in significantly reducing primary lesion severity and decreasing the number of satellite lesions. Topical 1% cyclic HPMPC and 1% phosphonoacetic acid were not quite as active as cidofovir. Ribavirin (5%) treatment reduced lesion severity and diminished the numbers of satellite lesions, but the mice died significantly sooner than placebos. 2-Amino-7-[(1,3,-dihydroxy-2-propoxy)methyl]purine (compound S2242; 1%) moderately reduced primary lesion sizes. Ineffective treatments included 5% arabinosyladenine, 1% arabinosylcytosine, 1% 5-chloro-arabinosylcytosine, 5% arabinosylhypoxanthine 5-monophosphate and 5% viramidine. Conclusions: Of the compounds tested, topically applied cidofovir was the most effective treatment of cutaneous vaccinia virus infections in immunosuppressed mice. Topical treatment with cidofovir could be considered as an adjunct to intravenous drug therapy for serious infections.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Topical Treatment of Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice with Selected Antiviral Substances

Smee

Bailey

Wong

et al. 2011

Antivir Chem Chemother

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“…The compound CMX001 (hexadecyloxypropyl CDV) has excellent activity against adenoviruses, orthopoxviruses, and polyomaviruses, as well as the herpesviruses (13,18,32,36). Equally important is the increased oral bioavailability conferred by the alkoxyalkyl substituent (1,3,17,30), which appears to reduce drug exposure in the mouse kidney and may reduce the potential of the drug for renal toxicity (4). While the discovery of truly broad spectrum antiviral drugs will be difficult, the development of CMX001 represents a significant advance.…”

mentioning

confidence: 99%

Inhibition of Herpesvirus Replication by 5-Substituted 4′-Thiopyrimidine Nucleosides

Prichard

Quenelle

Hartline

et al. 2009

Antimicrob Agents Chemother

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A series of 4-thionucleosides were synthesized and evaluated for activities against orthopoxviruses and herpesviruses. We reported previously that one analog, 5-iodo-4-thio-2-deoxyuridine (4-thioIDU), exhibits good activity both in vitro and in vivo against two orthopoxviruses. This compound also has good activity in cell culture against many of the herpesviruses. It inhibited the replication of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus with 50% effective concentrations (EC 50 s) of 0.1, 0.5, and 2 M, respectively. It also inhibited the replication of human cytomegalovirus (HCMV) with an EC 50 of 5.9 M but did not selectively inhibit Epstein-Barr virus, human herpesvirus 6, or human herpesvirus 8. While acyclovir-resistant strains of HSV-1 and HSV-2 were comparatively resistant to 4-thioIDU, it retained modest activity (EC 50 s of 4 to 12 M) against these strains. Some ganciclovir-resistant strains of HCMV also exhibited reduced susceptibilities to the compound, which appeared to be related to the specific mutations in the DNA polymerase, consistent with the observed incorporation of the compound into viral DNA. The activity of 4-thioIDU was also evaluated using mice infected intranasally with the MS strain of HSV-2. Although there was no decrease in final mortality rates, the mean length of survival after inoculation increased significantly (P < 0.05) for all animals receiving 4-thioIDU. The findings from the studies presented here suggest that 4-thioIDU is a good inhibitor of some herpesviruses, as well as orthopoxviruses, and this class of compounds warrants further study as a therapy for infections with these viruses.

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“…Since the use of VIG can be considered late prophylaxis or early treatment in our model, the high levels of antibodies being administered may delay or limit infection to the extent that innate effectors are sufficient for clearance of virus. The precise mechanism of action of VIG is not known; however, the correlation between primary lesion regression and survival and the benefits of topical over parenteral cidofovir support Neyts' contention that the skin is an important platform for the eventual spread of vaccinia virus to organs (25,30,37). The vaccinia virus dose-response relationship to survival in mice treated with the same dose of VIG suggests that early antibody treatment limits virus spread from the skin and also that early postexposure prophylaxis in humans, as soon as immunocompromised status is recognized and when the viral burden is relatively light, may be prudent.…”

Section: Discussionmentioning

confidence: 99%

Postexposure Prevention of Progressive Vaccinia in SCID Mice Treated with Vaccinia Immune Globulin

Fisher

Reed

Snoy

et al. 2011

Clin Vaccine Immunol

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Cutaneous infections of mice with vaccinia or cowpox viruses and efficacy of cidofovir

Cited by 36 publications

References 25 publications

Topical Treatment of Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice with Selected Antiviral Substances

Topical Treatment of Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice with Selected Antiviral Substances

Inhibition of Herpesvirus Replication by 5-Substituted 4′-Thiopyrimidine Nucleosides

Postexposure Prevention of Progressive Vaccinia in SCID Mice Treated with Vaccinia Immune Globulin

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