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  1. Article ; Online: Treatment of Vaccinia and Cowpox Virus Infections in Mice with CMX001 and ST-246.

    Quenelle, Debra C / Kern, Earl R

    Viruses

    2010  Volume 2, Issue 12, Page(s) 2681–2695

    Abstract: Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further ... ...

    Abstract Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further development. One of the most commonly used animal models for the confirmation of this activity has been the use of mice infected with either vaccinia or cowpox viruses. These model systems have the advantage that they are relatively inexpensive, readily available and do not require any special containment facilities; therefore, relatively large numbers of compounds can be evaluated in vivo for their activity. The two antiviral agents that have progressed from preclinical studies to human safety trials for the treatment of orthopoxvirus infections are the cidofovir analog, CMX001, and an inhibitor of extracellular virus formation, ST-246. These compounds are the ones most likely to be used in the event of a bioterror attack. The purpose of this communication is to review the advantages and disadvantages of using mice infected with vaccinia and cowpox virus as surrogate models for human orthopoxvirus infections and to summarize the activity of CMX001 and ST-246 in these model infections.
    Language English
    Publishing date 2010-12-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v2122681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Anti-HSV activity of serpin antithrombin III.

    Quenelle, Debra C / Hartman, Tracy L / Buckheit, Robert W / Prichard, Mark N / Lynn, Ralf Geiben

    International trends in immunity

    2014  Volume 2, Issue 2, Page(s) 87–92

    Abstract: Natural serine protease inhibitors (serpins) elicit sensing of a microbial cell intruder and activate an intrinsic cellular immune response in HIV and HCV infected cells. Here, we ... ...

    Abstract Natural serine protease inhibitors (serpins) elicit sensing of a microbial cell intruder and activate an intrinsic cellular immune response in HIV and HCV infected cells. Here, we demonstrate
    Language English
    Publishing date 2014-08-21
    Publishing country United States
    Document type Journal Article
    ISSN 2326-3121
    ISSN 2326-3121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis.

    Quenelle, Debra C / Birkmann, Alexander / Goldner, Thomas / Pfaff, Tamara / Zimmermann, Holger / Bonsmann, Susanne / Collins, Deborah J / Rice, Terri L / Prichard, Mark N

    Antiviral research

    2017  Volume 149, Page(s) 1–6

    Abstract: Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 ... ...

    Abstract Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30 mg/kg reduced mortality (P < 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3 mg/kg increased survival (P < 0.005). With HSV-2, MS infected mice, all dosages higher than the 0.3 mg/kg dose of pritelivir were effective (P < 0.005). For acyclovir resistant HSV-2, strain 12247, pritelivir dosages of 1-3 mg/kg significantly improved survival (P < 0.0001). Combination therapies of pritelivir at 0.1 or 0.3 mg/kg/dose with acyclovir (10 mg/kg/dose) were protective (P < 0.0001) when compared to the vehicle treated group against HSV-2, strain MS (in line with previous data using HSV-1). An increased mean days to death (P < 0.05) was also observed and was indicative of a potential synergy. Pharmacokinetic studies were performed to determine pritelivir concentrations and a dose dependent relationship was found in both plasma and brain samples regardless of infection status or time of initiation of dosing. In summary, pritelivir was shown to be active when treatment was delayed to 72 h post viral inoculation and appeared to synergistically inhibit mortality in this model in combination with acyclovir. We conclude pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis.
    MeSH term(s) Acyclovir/administration & dosage ; Acyclovir/pharmacokinetics ; Acyclovir/pharmacology ; Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; Disease Models, Animal ; Drug Therapy, Combination ; Encephalitis, Herpes Simplex/drug therapy ; Encephalitis, Herpes Simplex/mortality ; Encephalitis, Herpes Simplex/pathology ; Encephalitis, Herpes Simplex/virology ; Female ; Humans ; Mice ; Pyridines/administration & dosage ; Pyridines/pharmacokinetics ; Pyridines/pharmacology ; Sulfonamides ; Thiazoles/administration & dosage ; Thiazoles/pharmacokinetics ; Thiazoles/pharmacology ; Tissue Distribution ; Treatment Outcome
    Chemical Substances Antiviral Agents ; Pyridines ; Sulfonamides ; Thiazoles ; pritelivir (07HQ1TJ4JE) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2017-11-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2017.11.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Treatment of Vaccinia and Cowpox Virus Infections in Mice with CMX001 and ST-246

    Earl R. Kern / Debra C. Quenelle

    Viruses, Vol 2, Iss 12, Pp 2681-

    2010  Volume 2695

    Abstract: Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further ... ...

    Abstract Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further development. One of the most commonly used animal models for the confirmation of this activity has been the use of mice infected with either vaccinia or cowpox viruses. These model systems have the advantage that they are relatively inexpensive, readily available and do not require any special containment facilities; therefore, relatively large numbers of compounds can be evaluated in vivo for their activity. The two antiviral agents that have progressed from preclinical studies to human safety trials for the treatment of orthopoxvirus infections are the cidofovir analog, CMX001, and an inhibitor of extracellular virus formation, ST-246. These compounds are the ones most likely to be used in the event of a bioterror attack. The purpose of this communication is to review the advantages and disadvantages of using mice infected with vaccinia and cowpox virus as surrogate models for human orthopoxvirus infections and to summarize the activity of CMX001 and ST-246 in these model infections.
    Keywords vaccinia virus ; cowpox virus ; murine model ; orthopoxvirus ; antiviral ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2010-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency.

    Liang, Yu / Quenelle, Debra / Vogel, Jodi L / Mascaro, Cristina / Ortega, Alberto / Kristie, Thomas M

    mBio

    2013  Volume 4, Issue 1, Page(s) e00558–12

    Abstract: Cellular processes requiring access to the DNA genome are regulated by an overlay of epigenetic modifications, including histone modification and chromatin remodeling. Similar to the cellular host, many nuclear DNA viruses that depend upon the host cell' ... ...

    Abstract Cellular processes requiring access to the DNA genome are regulated by an overlay of epigenetic modifications, including histone modification and chromatin remodeling. Similar to the cellular host, many nuclear DNA viruses that depend upon the host cell's transcriptional machinery are also subject to the regulatory impact of chromatin assembly and modification. Infection of cells with alphaherpesviruses (herpes simplex virus [HSV] and varicella-zoster virus [VZV]) results in the deposition of nucleosomes bearing repressive histone H3K9 methylation on the viral genome. This repressive state is modulated by the recruitment of a cellular coactivator complex containing the histone H3K9 demethylase LSD1 to the viral immediate-early (IE) gene promoters. Inhibition of the activity of this enzyme results in increased repressive chromatin assembly and suppression of viral gene expression during lytic infection as well as reactivation from latency in a mouse ganglion explant model. However, available small-molecule LSD1 inhibitors are not originally designed to inhibit LSD1, but rather monoamine oxidases (MAO) in general. Thus, their specificity for and potency to LSD1 is low. In this study, a novel specific LSD1 inhibitor was identified that potently repressed HSV IE gene expression, genome replication, and reactivation from latency. Importantly, the inhibitor also suppressed primary infection of HSV in vivo in a mouse model. Based on common control of a number of DNA viruses by epigenetic modulation, it was also demonstrated that this LSD1 inhibitor blocks initial gene expression of the human cytomegalovirus and adenovirus type 5. IMPORTANCE Epigenetic mechanisms, including histone modification and chromatin remodeling, play important regulatory roles in all cellular processes requiring access to the genome. These mechanisms are often altered in disease conditions, including various cancers, and thus represent novel targets for drugs. Similarly, many viral pathogens are regulated by an epigenetic overlay that determines the outcome of infection. Therefore, these epigenetic targets also represent novel antiviral targets. Here, a novel inhibitor was identified with high specificity and potency for the histone demethylase LSD1, a critical component of the herpes simplex virus (HSV) gene expression paradigm. This inhibitor was demonstrated to have potent antiviral potential in both cultured cells and animal models. Thus, in addition to clearly demonstrating the critical role of LSD1 in regulation of HSV infection, as well as other DNA viruses, the data extends the therapeutic potential of chromatin modulation inhibitors from the focused field of oncology to the arena of antiviral agents.
    MeSH term(s) Adenoviridae/drug effects ; Adenoviridae/physiology ; Animals ; Antiviral Agents/metabolism ; Cell Line ; Cytomegalovirus/drug effects ; Cytomegalovirus/physiology ; Disease Models, Animal ; Female ; Herpes Simplex/drug therapy ; Histone Demethylases/antagonists & inhibitors ; Host-Pathogen Interactions/drug effects ; Humans ; Mice ; Mice, Inbred BALB C ; Simplexvirus/drug effects ; Simplexvirus/growth & development ; Simplexvirus/physiology ; Viral Load ; Virus Activation/drug effects ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; Histone Demethylases (EC 1.14.11.-) ; KDM1A protein, human (EC 1.5.-)
    Language English
    Publishing date 2013-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.00558-12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Synthesis and antiviral activity of 6-deoxycyclopropavir, a new prodrug of cyclopropavir.

    Li, Chengwei / Quenelle, Debra C / Prichard, Mark N / Drach, John C / Zemlicka, Jiri

    Bioorganic & medicinal chemistry

    2012  Volume 20, Issue 8, Page(s) 2669–2674

    Abstract: ... E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. et al. Antimicrob ...

    Abstract Synthesis of 6-deoxycyclopropavir (10), a prodrug of cyclopropavir (1) and its in vitro and in vivo antiviral activity is described. 2-Amino-6-chloropurine methylenecyclopropane 13 was transformed to its 6-iodo derivative 14 which was reduced to prodrug 10. It is converted to cyclopropavir (1) by the action of xanthine oxidase and this reaction can also occur in vivo. Compound 10 lacked significant in vitro activity against human cytomegalovirus (HCMV), human herpes virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus type 1 (HIV-1), human hepatitis B virus (HBV), Epstein-Barr virus (EBV), vaccinia virus and cowpox virus. In contrast, prodrug 10 given orally was as active as cyclopropavir (1) reported previously [Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. et al. Antimicrob. Agents Chemother. 2004, 48, 4745] against murine cytomegalovirus (MCMV) infection in mice and against HCMV in severe combined immunodeficient (SCID) mice.
    MeSH term(s) Administration, Oral ; Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/chemical synthesis ; Antiviral Agents/pharmacology ; Cowpox virus/drug effects ; Cyclopropanes/chemical synthesis ; Cyclopropanes/chemistry ; Cyclopropanes/pharmacology ; Cytomegalovirus/drug effects ; Guanine/analogs & derivatives ; Guanine/chemical synthesis ; Guanine/chemistry ; Guanine/pharmacology ; HIV-1/drug effects ; Hepatitis B virus/drug effects ; Herpesvirus 1, Human/drug effects ; Herpesvirus 2, Human/drug effects ; Herpesvirus 4, Human/drug effects ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Microbial Sensitivity Tests ; Molecular Structure ; Prodrugs/administration & dosage ; Prodrugs/chemical synthesis ; Prodrugs/pharmacology ; Vaccinia virus/drug effects
    Chemical Substances 6-deoxycyclopropavir ; Antiviral Agents ; Cyclopropanes ; Prodrugs ; Guanine (5Z93L87A1R)
    Language English
    Publishing date 2012-02-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2012.02.031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: In vitro and in vivo evaluation of isatin-beta-thiosemicarbazone and marboran against vaccinia and cowpox virus infections.

    Quenelle, Debra C / Keith, Kathy A / Kern, Earl R

    Antiviral research

    2006  Volume 71, Issue 1, Page(s) 24–30

    Abstract: It has been reported previously that some thiosemicarbazone compounds have prophylactic activity against smallpox disease and therapeutic activity against vaccinia virus (VV) infections. In these studies, isatin-beta-thiosemicarbazone (IBT) and marboran ... ...

    Abstract It has been reported previously that some thiosemicarbazone compounds have prophylactic activity against smallpox disease and therapeutic activity against vaccinia virus (VV) infections. In these studies, isatin-beta-thiosemicarbazone (IBT) and marboran were administered once daily by intraperitoneal (ip) injection to mice using 30, 10 or 3 mg/kg for 5 days beginning 24, 48 or 72 h after inoculation with VV or cowpox virus (CV). Both compounds were highly effective (p < 0.01) at preventing mortality due to VV even when treatment was delayed up to 72 h postinfection. In CV-infected mice, neither IBT nor Marboran were effective in preventing mortality at any dosage tested when administered at 24 h postinoculation. Viral replication in liver, spleen and kidney was delayed or reduced by 100-to 10,000-fold by 10 mg/kg of marboran, but not IBT, in VV infections. Neither compound was effective against CV infection. Neither IBT nor marboran treatment of mice cutaneously infected with VV or CV reduced viral replication or clinical disease. These results suggest that this class of compound has little therapeutic potential for orthopoxvirus infections since the in vivo activity against CV, a surrogate virus for variola, is lacking.
    MeSH term(s) Animals ; Antibodies, Viral/blood ; Antiviral Agents/pharmacology ; Cowpox virus/physiology ; Female ; Hydrazones/pharmacology ; Indoles/pharmacology ; Methisazone/pharmacology ; Mice ; Mice, Hairless ; Mice, Inbred BALB C ; Poxviridae Infections/drug therapy ; Poxviridae Infections/virology ; Statistics, Nonparametric ; Survival Analysis ; Vaccinia virus/physiology ; Virus Replication/drug effects
    Chemical Substances Antibodies, Viral ; Antiviral Agents ; Hydrazones ; Indoles ; isatine-beta-thiocarbohydrazone ; Methisazone (K3QML4J07E)
    Language English
    Publishing date 2006-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2006.02.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Efficacy of orally administered low dose N-methanocarbathymidine against lethal herpes simplex virus type-2 infections of mice.

    Quenelle, Debra C / Collins, Deborah J / Rice, Terri L / Rahman, Aquilur / Glazer, Robert

    Antiviral chemistry & chemotherapy

    2011  Volume 22, Issue 3, Page(s) 131–137

    Abstract: ... the antiviral activity of N-MCT was assessed against herpes simplex virus type-2 (HSV-2) in BALB/c mice ... Methods: BALB/c mice were infected intranasally with a lethal challenge dose of HSV-2. N-MCT was ...

    Abstract Background: N-methanocarbathymidine (N-MCT) has previously been shown to be effective against lethal orthopoxvirus and herpes simplex virus type-1 infections in mice. In this investigation, the antiviral activity of N-MCT was assessed against herpes simplex virus type-2 (HSV-2) in BALB/c mice.
    Methods: BALB/c mice were infected intranasally with a lethal challenge dose of HSV-2. N-MCT was administered orally twice daily to mice using doses of 0.01 to 100 mg/kg to determine effects on survival and on viral replication in organ and central nervous system (CNS) samples.
    Results: N-MCT provided significant protection from mortality even when treatments were delayed until 3 days after viral infection. Viral replication in organ and CNS samples from N-MCT-treated mice was reduced below the limit of detection after 4 days of treatment.
    Conclusions: These results indicated that low dose N-MCT treatment was more effective than acyclovir therapy. N-MCT may be effective against HSV disease in humans and is currently undergoing preclinical evaluation. In particular, its potential use as a combination therapy for HSV, with its differing metabolism from acyclovir, make it a promising compound to develop for human use.
    MeSH term(s) Administration, Oral ; Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Herpes Simplex/drug therapy ; Herpes Simplex/virology ; Herpesvirus 2, Human/drug effects ; Humans ; Mice ; Mice, Inbred BALB C ; Survival Rate ; Thymidine/administration & dosage ; Thymidine/analogs & derivatives ; Thymidine/pharmacology
    Chemical Substances Antiviral Agents ; (north)-methanocarbathymidine (LTM5S02010) ; Thymidine (VC2W18DGKR)
    Language English
    Publishing date 2011-11-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1033586-9
    ISSN 2040-2066 ; 0956-3202
    ISSN (online) 2040-2066
    ISSN 0956-3202
    DOI 10.3851/IMP1901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: CMX001 potentiates the efficacy of acyclovir in herpes simplex virus infections.

    Prichard, Mark N / Kern, Earl R / Hartline, Caroll B / Lanier, E Randall / Quenelle, Debra C

    Antimicrobial agents and chemotherapy

    2011  Volume 55, Issue 10, Page(s) 4728–4734

    Abstract: Although acyclovir (ACV) has proven to be of value in the therapy of certain herpes simplex virus (HSV) infections, there is a need for more effective therapies, particularly for serious infections in neonates and immunocompromised individuals, where ... ...

    Abstract Although acyclovir (ACV) has proven to be of value in the therapy of certain herpes simplex virus (HSV) infections, there is a need for more effective therapies, particularly for serious infections in neonates and immunocompromised individuals, where resistance to this drug can be problematic. CMX001 is an orally bioavailable lipid conjugate of cidofovir that is substantially less nephrotoxic than the parent drug and has excellent antiviral activity against all the human herpesviruses. This compound retains full antiviral activity against ACV-resistant laboratory and clinical isolates. The combined efficacy of CMX001 and ACV was evaluated in a new real-time PCR combination assay, which demonstrated that the combination synergistically inhibited the replication of HSV in cell culture. This was also confirmed in murine models of HSV infection, where the combined therapy with these two drugs synergistically reduced mortality. These results suggest that CMX001 may be effective in the treatment of ACV-resistant HSV infections and as an adjunct therapy in individuals with suboptimal responses to ACV.
    MeSH term(s) Acyclovir/pharmacology ; Acyclovir/therapeutic use ; Acyclovir/toxicity ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/toxicity ; Cells, Cultured ; Cytosine/analogs & derivatives ; Cytosine/pharmacology ; Cytosine/therapeutic use ; Cytosine/toxicity ; Drug Resistance, Viral ; Drug Synergism ; Drug Therapy, Combination ; Female ; Herpes Simplex/drug therapy ; Herpes Simplex/virology ; Herpesvirus 1, Human/drug effects ; Herpesvirus 2, Human/drug effects ; Humans ; Mice ; Mice, Inbred BALB C ; Organophosphonates/pharmacology ; Organophosphonates/therapeutic use ; Organophosphonates/toxicity
    Chemical Substances Antiviral Agents ; Organophosphonates ; brincidofovir (6794O900AX) ; Cytosine (8J337D1HZY) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2011-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00545-11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Cutaneous infections of mice with vaccinia or cowpox viruses and efficacy of cidofovir.

    Quenelle, Debra C / Collins, Deborah J / Kern, Earl R

    Antiviral research

    2004  Volume 63, Issue 1, Page(s) 33–40

    Abstract: Orthopoxviruses, including smallpox, monkeypox and molluscipox, pose risks to human health through bioterrorist acts or natural transmission. There is no approved therapy for orthopoxvirus infections; however, cidofovir (CDV) has been approved as an ... ...

    Abstract Orthopoxviruses, including smallpox, monkeypox and molluscipox, pose risks to human health through bioterrorist acts or natural transmission. There is no approved therapy for orthopoxvirus infections; however, cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of adverse effects following smallpox vaccination. For evaluation of new therapies directed against orthopoxvirus infections, we have utilized immunocompetent, hairless mice (SKH-1) inoculated by a cutaneous route with cowpox virus (CV) or vaccinia virus (VV). Mice subsequently developed skin lesions and virus was recovered from the site of inoculation and quantified. Skin biopsies were evaluated microscopically, revealing brick-like eosinophilic, intracytoplasmic inclusion bodies characteristic of orthopoxvirus infection. SKH-1 mice fully recovered from either CV or VV infection. Immunodeficient Athymic or Rhino mice inoculated with CV or VV had more lesions and severe disease than SKH-1 mice. CV-infected SKH-1 mice were treated either with systemic or topical CDV. Although some protection was achieved with systemic treatment, 5% topical CDV was most effective at reducing virus titers in skin, lung, kidney, and spleen. These models may provide a means for evaluating efficacy of new therapies directed against orthopoxvirus diseases and further confirm the topical activity of CDV against cutaneous infections.
    MeSH term(s) Administration, Cutaneous ; Animals ; Antiviral Agents/pharmacology ; Cidofovir ; Cowpox/drug therapy ; Cowpox/virology ; Cowpox virus/growth & development ; Cytosine/analogs & derivatives ; Cytosine/pharmacology ; Disease Models, Animal ; Mice ; Organophosphonates ; Organophosphorus Compounds/pharmacology ; Orthopoxvirus/drug effects ; Orthopoxvirus/growth & development ; Vaccinia/drug therapy ; Vaccinia/veterinary ; Vaccinia/virology ; Vaccinia virus/drug effects
    Chemical Substances Antiviral Agents ; Organophosphonates ; Organophosphorus Compounds ; Cytosine (8J337D1HZY) ; Cidofovir (JIL713Q00N)
    Language English
    Publishing date 2004-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2004.02.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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