brivudine and Herpes-Simplex

brivudine has been researched along with Herpes-Simplex* in 56 studies

Reviews

7 review(s) available for brivudine and Herpes-Simplex

ArticleYear
Review for Disease of the Year: Treatment of Viral Anterior Uveitis: A Perspective.
    Ocular immunology and inflammation, 2018, Volume: 26, Issue:7

    To define a clinically tailored therapeutic strategy for the treatment of viral anterior uveitis (VAU).. A PubMed search spanning the past 5 years was conducted using the MesH-terms "viral anterior uveitis" and "therapy.". The herpes simplex virus (HSV), the varicella zoster virus (VZV), and the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses, including rubella, chikungunya, and zika, have been linked with distinct forms of the disease. Depending on the causative agent and the host immunocompetence, the mainstay treatment for suspected VAU is a combination of topical or systemic antivirals and topical corticosteroids, supplemented with cycloplegics and intraocular-pressure-lowering medication.. Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.

    Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chikungunya Fever; Cytomegalovirus Infections; Eye Infections, Viral; Famciclovir; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Rubella; Uveitis, Anterior; Valacyclovir; Zika Virus Infection

2018
Antiviral therapy of herpes simplex and varicella-zoster virus infections.
    Intervirology, 1997, Volume: 40, Issue:5-6

    Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

    Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Arabinofuranosyluracil; Bromodeoxyuridine; Chickenpox; Drug Resistance, Microbial; Encephalitis, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Valacyclovir; Valine

1997
Promising new antiviral drugs.
    Journal of the American Academy of Dermatology, 1988, Volume: 18, Issue:1 Pt 2

    We now have a basis for a more rational approach to rapid evaluation and development of antiviral drugs by screening for activity in vitro, testing for toxicity and efficacy in animals, and clinical testing in humans. Acyclovir is a prototype of this improved process. Interferon has a beneficial effect against CMV infection in renal transplant patients and has promising results in the treatment of papillomas and rhinovirus infections. It does not seem to be as effective against genital herpes or varicella zoster as acyclovir. Ribavirin is effective against respiratory syncytial virus infections and Lassa fever. Varicella-zoster virus is highly sensitive to bromovinyl deoxyuridine in vitro. Phosphonoformate is effective in herpes simplex in animals but of little clinical benefit topically in human recurrent A2 herpes. Zidovudine may decrease mortality rates and infectious complications in patients with acquired immunodeficiency syndrome. DHPG (9-(1,3-dihydroxy-2-propoxymethyl]guanine is useful in treatment of cytomegalovirus and infection in immunocompromised patients. The prodrug of acyclovir results in high blood levels of acyclovir and shows promise in the treatment of varicella-zoster infections. Many halogenated pyrimidine nucleoside analogs are being developed. Buciclovir is another acyclic guanosine analog effective against herpes simplex virus in vitro. 2'-nor-cyclic guanosine monophosphate has a broad antiviral spectrum of action. Interleukin-2 is being investigated. Combined therapies of two or more antiviral drugs or antiviral drugs and other treatments are being studied.

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Interferons; Phosphonoacetic Acid; Ribavirin; Thymidine; Zidovudine

1988
[Therapy of herpes simplex encephalitis].
    Deutsche medizinische Wochenschrift (1946), 1988, Dec-16, Volume: 113, Issue:50

    Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain Edema; Bromodeoxyuridine; Dexamethasone; Drug Therapy, Combination; Encephalitis; Ganciclovir; Herpes Simplex; Humans; Immunoglobulins; Interferons; Vidarabine

1988
Herpes virus infections in patients with neoplastic disease. Diagnosis and therapy.
    The American journal of medicine, 1984, Volume: 76, Issue:3

    Herpes viruses are among the most common and troublesome opportunistic pathogens infecting patients with neoplastic diseases. The recent development of partially effective and relatively nontoxic antiviral agents offers promise for the prophylaxis or therapy of these infections in high-risk groups. Vidarabine and acyclovir have shown efficacy in several herpes virus infections and are now licensed in the United States. Alpha interferon may also be useful in the prophylaxis or early therapy of certain herpes virus infections. Newer antiviral agents and combination therapies are under study. Early and rapid diagnosis of such infections is critical to the development of effective therapy.

    Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cloning, Molecular; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infectious Mononucleosis; Interferons; Kidney Transplantation; Leukemia; Lymphopenia; Neoplasms; Pulmonary Fibrosis; Vidarabine

1984
Antiviral chemotherapy.
    The Medical journal of Australia, 1984, Jun-09, Volume: 140, Issue:12

    Progress in antiviral chemotherapy has taken place as a logical strategy for the design of antiviral agents has emerged. The second-generation nucleoside analogues, led by acyclovir, have proved their worth against herpesviruses and should now become a standard part of medical practice. Meanwhile, recombinant DNA technology has lowered the cost of interferons to the point at which the several human subtypes of these naturally occurring hormones can be subjected individually to controlled clinical trials against the viral diseases in the treatment of which they show promise. Yet, optimism about the future of antiviral chemotherapy must be tempered by the observation that most of the agents discussed in this review are described more accurately as promising rather than proven, and several of these have not yet been released in Australia at the time of writing.

    Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Bromodeoxyuridine; Female; Hepatitis B; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; In Vitro Techniques; Interferons; Male; Neoplasms; Papillomaviridae; Respiratory Tract Infections; Ribavirin; Rimantadine; Tumor Virus Infections; Vidarabine

1984
Recurrent herpes simplex: the outlook for systemic antiviral agents.
    British medical journal (Clinical research ed.), 1981, Jun-06, Volume: 282, Issue:6279

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Genes, Viral; Guanine; Herpes Simplex; Humans; Mice; Recurrence; Simplexvirus; Thymidine Kinase; Virus Replication

1981

Trials

2 trial(s) available for brivudine and Herpes-Simplex

ArticleYear
[Antiviral chemotherapy].
    Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde, 1986, Volume: 134, Issue:3

    After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

    Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

1986
Oral bromovinyldeoxyuridine therapy for herpes simplex and varicella-zoster virus infections in severely immunosuppressed patients: a preliminary clinical trial.
    Journal of medical virology, 1986, Volume: 18, Issue:1

    Twenty-five patients with haematological diseases were treated orally with the highly potent and selective anti-herpes agent, bromovinyldeoxyuridine (BVDU), in a dosage of 7.5 mg/kg/day (divided over three or four doses a day) for 5 days for an intercurrent mucocutaneous herpesvirus infection. Of these 25 patients, 8 were severely granulocytopenic at the time of the viral infection, and 12 recently had undergone bone-marrow transplantation; 5 were under cytotoxic therapy for a lymphoproliferative disorder; 13 had herpes simplex virus type 1 (HSV-1); 1 had herpes simplex virus type 2 (HSV-2); and 11 had varicella-zoster virus (VZV) infection. In all but two patients, BVDU arrested progression of the HSV or VZV infection within 1-2 days after treatment was started. One of the two patients who failed to respond to BVDU had an HSV-2 infection. The other had an HSV-1 infection, which was highly sensitive to BVDU in vitro; BVDU may have failed in this patient because of incomplete drug intake or profuse diarrhoea, or both. The results of this preliminary uncontrolled clinical trial suggest that BVDU may be an effective and safe drug for the oral treatment of HSV-1 and VZV infections in severely immunosuppressed patients.

    Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Bromodeoxyuridine; Child; Child, Preschool; Clinical Trials as Topic; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppression Therapy; Leukemia; Lymphoma; Male; Middle Aged

1986

Other Studies

47 other study(ies) available for brivudine and Herpes-Simplex

ArticleYear
Synthesis and anti-HSV activity of tricyclic penciclovir and hydroxybutylguanine derivatives.
    Bioorganic & medicinal chemistry, 2019, 03-15, Volume: 27, Issue:6

    A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R = 4-MeO-C

    Topics: Acyclovir; Antiviral Agents; Guanine; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Models, Molecular

2019
Emimycin and its nucleoside derivatives: Synthesis and antiviral activity.
    European journal of medicinal chemistry, 2018, Jan-20, Volume: 144

    The synthesis of emimycin, 5-substituted emimycin analogues and the corresponding ribo- and 2'-deoxyribonucleoside derivatives is described. Emimycin, its 5-substituted congeners and the ribonucleoside derivatives are completely devoid of antiviral activity against RNA viruses. In contrast, some of the 2'-deoxyribosyl emimycin derivatives are potent inhibitors of the replication of herpes simplex virus-1 and varicella-zoster virus, lacking cytotoxicity.

    Topics: Antiviral Agents; Cell Line; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Nucleosides; Pyrazines; Varicella Zoster Virus Infection; Virus Replication

2018
Single nucleotide polymorphisms of thymidine kinase and DNA polymerase genes in clinical herpes simplex virus type 1 isolates associated with different resistance phenotypes.
    Antiviral research, 2014, Volume: 107

    The role of mutations in the thymidine kinase (TK, UL23) and DNA polymerase (pol, UL30) genes of herpes simplex virus (HSV) for development of different resistance phenotypes has to be exactly determined before genotypic resistance testing can be implemented in patient's care. Furthermore, the occurrence of cross-resistance is of utmost clinical importance. In this study, clinical HSV-1 isolates obtained between 2004 and 2011 from 26 patients after stem cell transplantation were examined in parallel by phenotypic and genotypic resistance testing. Thirteen isolates, which were phenotypically cross-resistant to acyclovir (ACV), penciclovir (PCV) and brivudin (BVDU), exhibited consistently frameshift or non-synonymous mutations in the TK gene known to confer resistance. One of these mutations (insertion of C at the nucleotide positions 1061-1065) has not been described before. Seven strains, phenotypically resistant to ACV and PCV and, except one each, sensitive to BVDU and resistant to foscarnet (FOS), carried uniformly resistance-related substitutions in the DNA pol gene. Finally, 3 isolates, resistant to ACV, PCV and 2 out of these also resistant to BVDU, had known but also unclear substitutions in the TK and DNA pol genes, and 3 isolates were completely sensitive. In conclusion, clinical ACV-resistant HSV-1 isolates, carrying resistance-associated mutations in the TK gene, can be regarded as cross-resistant to other nucleoside analogs such as BVDU. In contrast, clinical FOS-resistant HSV-1 strains which are cross-resistant to ACV may be sensitive to BVDU. This has to be considered for drug changes in antiviral treatment in case of ACV resistance.

    Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Child; DNA-Directed DNA Polymerase; DNA, Viral; Drug Resistance, Viral; Exodeoxyribonucleases; Female; Frameshift Mutation; Guanine; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutagenesis, Insertional; Mutation, Missense; Point Mutation; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Thymidine Kinase; Viral Proteins; Young Adult

2014
Novel resistance-associated mutations of thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 and type 2.
    Antiviral therapy, 2011, Volume: 16, Issue:8

    Studies to verify correlations between phenotypes and genotypes of herpes simplex virus (HSV) are an important tool to establish a database of resistance-associated mutations.. In this study, 32 acyclovir (ACV)-resistant clinical HSV-1 and 4 ACV-resistant clinical HSV-2 isolates were examined in parallel by both phenotypic and genotypic resistance testing. Additionally, five non-viable HSV-1 strains and two non-viable HSV-2 strains with clinical resistance were included in genotypic resistance analysis.. All ACV-resistant HSV isolates showed cross-resistance to brivudin and penciclovir, and were sensitive to foscarnet and cidofovir. Acyclovir resistance was assigned to frameshift and single non-synonymous mutations of the thymidine kinase (TK) gene in 32 out of 37 HSV-1 strains and in 4 out of 6 HSV-2 strains. In three HSV-1 isolates, there were resistance-associated amino acid substitutions of the DNA polymerase (pol). Six substitutions in the TK and two in the DNA pol gene could not be attributed without doubt to either ACV resistance or natural gene polymorphism. Altogether, 10 resistance-related mutations in the TK and 1 in the DNA pol gene have not been reported previously.. The novel non-synonymous mutations found in this study enrich the knowledge about the genetic alterations of TK and DNA pol genes in ACV-resistant clinical HSV strains. Together with data from the literature, the findings justify the generation of a HSV database that contains resistance mutations associated with ACV resistance phenotype.

    Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Child; Child, Preschool; Cidofovir; Cytosine; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Foscarnet; Genotype; Guanine; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Male; Middle Aged; Mutation; Organophosphonates; Sequence Analysis, DNA; Thymidine Kinase; Viral Proteins

2011
Acute hepatitis due to brivudin: a case report.
    Journal of hepatology, 2009, Volume: 51, Issue:5

    Brivudin is licensed in several European countries for the treatment of herpetic infections, and is considered safe (approximately 1% of patients with transient elevation of liver enzymes) in large multicenter trials.. We report a case of acute brivudin hepatitis documented with a liver biopsy in detail.. Liver biopsy demonstrated acute liver injury with a predominant cytolytic pattern and features suggestive of a drug-induced immunoallergic hepatitis. Elevated ALT levels returned to normal within weeks.. This is the first published case of acute immunoallergic hepatitis due to brivudin.

    Topics: Adult; Alanine Transaminase; Antiviral Agents; Bilirubin; Bromodeoxyuridine; Chemical and Drug Induced Liver Injury; Herpes Simplex; Humans; Male

2009
Synthesis and antiviral activity of 5-thien-2-yl-2'-deoxyuridine analogues.
    Journal of medicinal chemistry, 1993, Mar-05, Volume: 36, Issue:5

    A number of 5-heteroaromatic-substituted 2'-deoxyuridines were synthesized from 5-iodo-2'-deoxyuridine using tetraorganotin reagents and palladium complexes as catalyst. The palladium-catalyzed cross-coupling reaction between 5-iodo-2'-deoxyuridine and stannylated heteroaromatics was optimized for the synthesis of the 5-thien-3-yl-2'-deoxyuridine and 5-furan-3-yl-2'-deoxyuridine. 5-(5-Iodothien-2-yl)-2'-deoxyuridine was used as starting material for the synthesis of 5-(5-methylthien-2-yl)-2'-deoxyuridine, 5-(5-vinylthien-2-yl)-2'-deoxyuridine, and 5-(5-ethynylthien-2-yl)-2'- deoxyuridine. 5-(5-Nitrothien-2-yl)-2'-deoxyuridine was synthesized using ceric ammonium nitrate as reagent. 5-(Isoxazol-5-yl)-2'-deoxyuridine was synthesized from 5-(3-oxopropyn-1-yl)-2'-deoxyuridine. Finally, 5-(5-chlorothien-2-yl)-beta-D-arabinofuranosyluracil and 5-(5-bromothien-2-yl)-beta-D-arabinofuranosyluracil were obtained by halogenation of 5-thien-2-yl-beta-D-arabinofuranosyluracil. Introduction of an alkyl substituent in the 5-position of the thienyl group of 5-thien-2-yl-2'-deoxyuridine or substitution of the 2-deoxyribofuranose ring by an arabinofuranose moiety gave decreased activity against HSV-1 and VZV replication when compared with the 5"-halogenated-5-thien-2-yl-2'-deoxyuridines. 5-(5-Bromothien-2-yl)-2'-deoxyuridine caused prompt healing of HSV-1 keratitis when administered as eye drops (0.2%) to rabbits.

    Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Deoxyuridine; Herpes Simplex; Herpesvirus 3, Human; Humans; Keratitis, Herpetic; Mice; Organotin Compounds; Palladium; Rabbits; Simplexvirus; Structure-Activity Relationship; Thiophenes; Virus Replication

1993
Antiviral activity of 5-iodo-2'-deoxyuridine and related drugs in human keratinocytes infected in vitro with herpes simplex virus type 1.
    Skin pharmacology : the official journal of the Skin Pharmacology Society, 1991, Volume: 4, Issue:4

    5-Iodo-2'-deoxyuridine (IUDR) is a potent topical antiviral agent in experimental animals but is less active in man for treating cutaneous viral infections. We have shown here that IUDR is 5 times less active in human keratinocytes infected in vitro with herpes simplex virus type 1 than in guinea pig embryo cells infected in culture. To account, in part, for this difference in activity of IUDR, we measured the capacity of these different cultures to catabolize and thus inactivate the drug. IUDR is catabolized by thymidine phosphorylase; activity of this enzyme was very high in human keratinocytes in vitro but was very low in guinea pig embryo cells. The antiviral activity of IUDR in human keratinocytes, however, was not increased by inhibiting thymidine phosphorylase; inhibiting thymidine phosphorylase apparently increased the availability of thymidine that would compete with IUDR and, indeed, the activity of IUDR in infected cells was reduced by addition of thymidine to the medium. These data indicate that the catabolism of IUDR and related analogs alters antiviral activity in human keratinocytes.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Drug Interactions; Guinea Pigs; Herpes Simplex; Humans; Idoxuridine; Keratinocytes; Simplexvirus; Thymidine; Thymidine Phosphorylase; Thymine; Zidovudine

1991
Synthesis and biological evaluation of some cyclic phosphoramidate nucleoside derivatives.
    Journal of medicinal chemistry, 1990, Volume: 33, Issue:9

    (E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in solution for it to be tested in vivo. The biological properties of this and some related derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine and acyclovir have been evaluated in in vitro and in vivo systems designed to show the effects of any intracellular liberation of the nucleotide. Although some of the derivatives are probably acting as prodrugs of the active nucleosides, there is no evidence for the liberation of meaningful concentrations of the 5'-nucleotide by any of the compounds.

    Topics: Animals; Antiviral Agents; Herpes Simplex; Humans; Mice; Mice, Nude; Prodrugs; Rabbits; Tumor Cells, Cultured

1990
Low levels of herpes simplex virus thymidine- thymidylate kinase are not limiting for sensitivity to certain antiviral drugs or for latency in a mouse model.
    Virology, 1989, Volume: 168, Issue:2

    Herpes simplex virus mutant KG111 contains a nonsense mutation at codon 44 of the viral thymidine kinase (tk) gene and produces low amounts of a truncated tk polypeptide. We tested mutant KG111 and related viruses that specify varying amounts of similar truncated tk polypeptides for their sensitivities to antiviral nucleoside analogs at different temperatures using plaque reduction assays. The results of these assays showed that the nonsense mutation confers high resistance to bromovinyldeoxyuridine (BVdU) at any temperature and temperature-dependent resistance to acyclovir (ACV), buciclovir (BCV), ganciclovir (DHPG), and fluoroiodoarabinouracil (FIAU). Above relatively low threshold levels of tk that varied depending on the drug tested, viruses exhibited full sensitivity to ACV, BCV, DHPG, and FIAU at 34 degrees. Below these threshold levels, however, decreases in drug sensitivity were linear with decreases in tk levels, forming the basis of a pharmacological assay for tk gene expression. Studies of thymidine (TdR) anabolism in infected 143 tk-cells showed that when high TdR concentrations were added to the medium, KG111 directed thymidine monophosphate (TMP) formation at rates consonant with the amount of tk polypeptide produced by the mutant. When low concentrations to TdR were added to the medium, however, KG111 directed TMP formation at a rate similar to that directed by wild-type virus, indicating that the truncation of the tk polypeptide had little or no effect on tk activity at 34 degrees. Subsequent anabolism to thymidine diphosphate and thymidine triphosphate was reduced in KG111-infected cells, indicating a defect in TMP kinase activity that explains this mutant's resistance to BVdU. Despite the low levels of tk and TMP kinase activity expressed by KG111, this mutant established reactivatable latent infections as efficiently as wild-type virus in a mouse model.

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Drug Resistance, Microbial; Herpes Simplex; Humans; Mice; Mutation; Nucleoside-Phosphate Kinase; Phosphotransferases; Simplexvirus; Temperature; Thymidine; Thymidine Kinase; Thymine Nucleotides; Trigeminal Ganglion; Tumor Cells, Cultured; Vero Cells

1989
5-(2-bromoethyl)-2'-deoxyuridine: a selective inhibitor of herpes simplex viruses in vitro.
    Clinical and experimental obstetrics & gynecology, 1989, Volume: 16, Issue:1

    A new pyrimidine analog, 5-(2-bromoethyl)-2'-deoxyuridine (BEUdR), was tested in vitro for antiviral activity on Herpes simplex virus types 1 and 2. As reference compounds, ACG, BVUdR and PAA were used. Compared to ACG and BVUdR, BEUdR resulted less potent on both HSV-1 and HSV-2. However, a 50% inhibition of the multiplication of uninfected cells could be obtained only at very high BEUdR concentration (ID50 = 8500 microM). This makes BEUdR the least toxic analog known and gives it a selective index comparable to, if not better, than of ACG and BVUdR.

    Topics: Antiviral Agents; Bromodeoxyuridine; Herpes Simplex; Humans

1989
Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity.
    Journal of medicinal chemistry, 1988, Volume: 31, Issue:9

    The synthesis of potential "combined prodrugs" wherein phosphonoformate or phosphonoacetate was attached to the 5'-position of 2'-deoxyuridine, 2'-deoxythymidine, 5-iodo-2'-deoxyuridine (IDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), or 5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or to the 3'-position of CEDU is described. The antiviral activities of these derivatives and of reference compounds were compared in Vero, HEp-2, and primary rabbit kidney cells against herpes simplex virus types 1 and 2 (HSV-1 and -2). The CEDU and BVDU analogues were also evaluated against systemic and intracutaneous HSV-1 infection in mice. The nature of the 5-substituent proved critical for antiviral activity, since only the 5-iodo-, 5-(2-bromovinyl)-, and 5-(2-chloroethyl)-substituted derivatives were inhibitory to the herpesviruses. Furthermore, the type specificity is determined by the nature of the 5-substituent: the IDU analogues were similarly inhibitory to HSV-1 and -2 whereas the CEDU and BVDU analogues inhibited HSV-2 replication only at considerably higher concentrations than HSV-1. In vivo, several derivatives were shown to possess significant antiviral activity; however, none surpassed its respective parent compound, CEDU or BVDU, in potency. It seems improbable, therefore, that a synergistic effect between PFA or PAA and the nucleoside analogue occurred. The extent of in vitro and in vivo activity of the CEDU and BVDU 5'-phosphonoformates and 5'-phosphonoacetates is most plausibly explained by the ease by which the "combined prodrugs" are hydrolyzed and the parent compound, CEDU and BVDU, respectively, is released.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chemical Phenomena; Chemistry; Deoxyuridine; Foscarnet; Herpes Simplex; Mice; Organophosphorus Compounds; Pharmaceutical Preparations; Phosphonoacetic Acid; Prodrugs; Rabbits; Simplexvirus; Thymidine; Vero Cells

1988
Synthesis and biological activity of 5-(2,2-difluorovinyl)-2'-deoxyuridine.
    Journal of medicinal chemistry, 1987, Volume: 30, Issue:8

    5-(2,2-Difluorovinyl)uracil (IV) was synthesized from 2,4-dimethoxy-5-bromopyrimidine by sequential formylation, difluoromethylenation, and removal of the 2- and 4-methyl groups. Condensation of the trimethylsilyl derivative of IV with protected D-erythro-pentofuranosyl chloride followed by separation of anomers and deblocking gave 5-(2,2-difluorovinyl)-2'-deoxyuridine (V). Compound V was active against herpes simplex virus type 1 (HSV-1) infection as well as tumor cells transformed by the HSV-1 thymidine kinase gene.

    Topics: Animals; Cell Line; Chemical Phenomena; Chemistry; Deoxyuridine; Herpes Simplex; Humans; Mice; Neoplasms, Experimental; Rabbits; Simplexvirus; Structure-Activity Relationship; Vaccinia virus; Viruses

1987
Therapeutic effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, caffeic acid oxidation product, and trisodiumphosphonoformate on cutaneous herpes simplex virus type 1 infection in guinea pigs.
    Journal of medical virology, 1987, Volume: 23, Issue:3

    The influence of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), caffeic acid oxidation product (KOP), and trisodiumphosphonoformate (TPF) on the course of the primary cutaneous herpes simplex virus infection was investigated by means of a guinea pig test model. The antiviral substances were applied in an ointment with 10% urea as a penetration mediator. When the treatment was initiated 15 minutes after virus inoculation, 3% BVDU effectively inhibited the development of herpetic vesicles and 0.1% BVDU prevented the appearance of herpetic satellites. Under the same conditions 1% and 3% KOP ointments inhibited the appearance of satellites; and 0.5% TPF ointment completely inhibited the development of cutaneous herpes lesions. Prophylactic drug administration given 24, 20, and 4 hours before virus inoculation was without any protective effect.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Caffeic Acids; Cinnamates; Female; Foscarnet; Guinea Pigs; Herpes Simplex; Humans; Male; Organophosphorus Compounds; Oxidation-Reduction; Phosphonoacetic Acid; Simplexvirus

1987
Comparative metabolism of E-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in herpes simplex virus-infected cells.
    Molecular pharmacology, 1987, Volume: 31, Issue:4

    The antiviral activities and metabolic fates of E-5-(2-bromovinyl)-2'-deoxyuridine (BrVdUrd) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BrVaraUra) were compared in a dThd kinase-deficient human fibroblast cell line, infected with parental strains of herpes simplex virus, and other strains expressing no viral dThd kinase activity. Metabolic experiments were performed at concentrations well above the ID50 for each compound because radiolabeled agents were not available. BrVaraUra and its nucleotides qualitatively displayed chromatographic and anabolic characteristics which closely paralleled those of BrVdUrd and its nucleotides. Monophosphorylation of both drugs was dependent upon the presence of viral dThd kinase activity except in the case of one dThd kinase-negative type 1 mutant (SC16R5C1) which retained BrVdUrd/BrVaraUra kinase activity. Intracellular uptake of either parent compound was absent during mock-infection and minimal in the cases of infection with mutants unable to phosphorylate the parent compound. Parental type 1 strains were able to induce diphosphorylation and triphosphorylation of both compounds to a similar, dose-dependent degree. Extracts of type 2-infected cells contained greater quantities of BrVdUrd and its monophosphate compared with BrVaraUra and its monophosphate, after identical drug exposure and infection conditions. As previously observed for BrVdUrd, diphosphorylated and triphosphorylated nucleotides of BrVaraUra were not detected after type 2 infection. BrVdUrd and BrVaraUra metabolic breakdown pathways differed, however, as evidenced by the formation of E-5-(2-bromovinyl)uracil (BrVUra). Unlike BrVdUrd, BrVaraUra formed no BrVUra in infected cells, suggesting that replacement of 2'-deoxyribose with arabinose makes the compound biologically more stable, presumably because of resistance to enzymatic breakdown by pyrimidine nucleoside phosphorylases. In this dThd kinase-negative cell line, BrVdUrd and BrVaraUra displayed qualitatively similar susceptibility profiles in that activities were type 1 selective and dThd kinase dependent. Antiviral activities against dThd kinase-positive type 1 strains were similar with both compounds. These data would suggest that BrVdUrd and BrVaraUra have identical type-specific dThd-dTMP kinase-dependent mechanisms of cellular uptake and phosphorylation, but that the latter is not subjected to phosphorolysis and resultant formation of an inactive metabolite. Furthermore, the absenc

    Topics: Arabinofuranosyluracil; Bromodeoxyuridine; Cell Line; Chromatography, High Pressure Liquid; Fibroblasts; Herpes Simplex; Humans; Osteosarcoma; Uridine

1987
Combined antiviral effects of acyclovir or bromovinyldeoxyuridine and human immunoglobulin in herpes simplex virus-infected mice.
    Antiviral research, 1987, Volume: 7, Issue:4

    Suboptimal dosage regimens of antivirals (acyclovir or bromovinyldeoxyuridine) and human immunoglobulin have been combined in the treatment of hairless mice infected with herpes simplex virus type 1. The aim of this study was to establish how late after infection human immunoglobulin could be given to still be effective and for how long would the protective effect last. The combination of acyclovir or bromovinyldeoxyuridine with passive immunization proved additive or even synergistic depending on the time of immunoglobulin administration and the observation period after infection. When the survival rate of the mice was followed for up to 20 days postinfection, synergistic action seemed to occur with immunoglobulin given as late as 2 or 3 days after infection. When the mice were followed for up to 100 days after infection, however, it turned out that only the immunoglobulin given 4 h after infection led to a synergistic effect with the antivirals. Most of the mice subjected to combined treatment, in contrast to mice treated with the antivirals only, did not develop anti-HSV antibodies. This lack of a specific humoral immune response possibly reflects the rapid inhibition of virus replication early after challenge by the combined treatment, thus preventing the production of a sufficient amount of viral antigen in the body needed for a measurable antibody induction.

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Combined Modality Therapy; Drug Administration Schedule; Drug Synergism; Herpes Simplex; Humans; Immunization, Passive; Mice; Mice, Hairless

1987
Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridine.
    Journal of medicinal chemistry, 1986, Volume: 29, Issue:2

    (E)-5-(2-Bromovinyl)uracil (BVU) and (E)-5-(2-bromovinyl)uridine (BVRU) were synthesized starting from 5-formyluracil via (E)-5-(2-carboxyvinyl)uracil or starting from 5-iodouridine via (E)-5-(2-carbomethoxyvinyl)uridine and (E)-5-(2-carboxyvinyl)uridine, respectively. Depending on the choice of the cell system, BVU and BVRU exhibited a marked activity against herpes simplex virus type 1 (HSV-1) in vitro. Although BVU and BVRU were less potent than the reference compound (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), their antiviral activity spectrum was remarkably similar to that of BVDU. The latter findings suggest that BVU and BVRU are metabolically converted to BVDU or a phosphorylated product thereof. In vivo, BVU protected mice against a lethal disseminated HSV-1 infection.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Bromouracil; Deoxyuridine; Herpes Simplex; Mice; Mice, Inbred BALB C; Rabbits; Simplexvirus; Thymine; Uridine; Virus Replication

1986
Prolonged herpes simplex virus latency in vitro after treatment of infected cells with acyclovir and human leukocyte interferon.
    Antimicrobial agents and chemotherapy, 1986, Volume: 29, Issue:4

    We previously demonstrated that herpes simplex virus type 1 (HSV-1) can be established in a latent form in vitro by the treatment of HSV-infected human cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) in combination with human leukocyte interferon (IFN-alpha). We now report that the substitution of BVDU with 9-[(2-hydoxyethoxy)methyl]guanine (acyclovir; ACV) during a combined treatment with IFN-alpha inhibited HSV-1 replication and established in vitro virus latency that could be maintained for a longer period after inhibitor removal and a continued incubation at 37 degrees C. By contrast, the treatment of HSV-1-infected cells with combined IFN-alpha and 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a congener of ACV, failed to establish in vitro virus latency. Furthermore, none of these inhibitors used alone was sufficient to establish in vitro virus latency. The use of nucleoside analogs differing from BVDU in their modes of action has enabled us to initiate studies designed to extend in vitro virus latency.

    Topics: Acyclovir; Bromodeoxyuridine; Cell Line; Cell Survival; DNA, Viral; Drug Synergism; Herpes Simplex; Humans; Interferon Type I; Nucleosides; Simplexvirus; Time Factors; Virus Replication

1986
Treatment of experimental herpes simplex virus type 1 encephalitis in mice with (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil: comparison with bromovinyl-deoxyuridine and acyclovir.
    Antiviral research, 1986, Volume: 6, Issue:2

    The efficiency of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) as inhibitors of three herpes simplex virus type 1 (HSV-1) strains was assessed in comparison to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR), 9-(2-hydroxyethoxymethyl)guanine (ACV), and trisodium phosphonoformate (Na3PFA) using a plaque assay in human embryonic lung fibroblast (HELF) cell cultures. The following order of decreasing activity was found: BrVaraU greater than VaraU greater than BrVU-dR greater than ACV much greater than Na3PFA. In HELF cell cultures, the selectivity indexes of VaraU and BrVaraU were 10 times higher than those of BrVUdR and ACV. Protection of mice from encephalitis and death due to intracerebral (i.c.) infection with a clinical HSV-1 isolate was nearly complete if mice were treated intraperitoneally (i.p.) with two daily doses of VaraU and BrVaraU (100 or 200 mg/kg per day) over a period of 5 or 10 days. The efficacy was similar to ACV, but, using a treatment schedule of three daily i.p. doses over 10 days, with equimolar amounts of the nucleoside analogs, VaraU and BrVaraU (140 and 180 mg/kg per day) were superior to ACV (130 mg/kg per day) (P less than 0.05).

    Topics: Acyclovir; Animals; Arabinofuranosyluracil; Bromodeoxyuridine; Cells, Cultured; Encephalitis; Female; Foscarnet; Herpes Simplex; Humans; Mice; Phosphonoacetic Acid; Simplexvirus; Uridine; Viral Plaque Assay

1986
Therapeutic use of newer antiviral agents.
    International journal of cell cloning, 1986, Volume: 4 Suppl 1

    Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cytomegalovirus; DNA, Viral; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Simplexvirus

1986
Efficacy of topical treatment for herpes simplex virus infections: predictions from an index of drug characteristics in vitro.
    The Journal of infectious diseases, 1986, Volume: 153, Issue:1

    Topical antiviral treatments for recurrent infection with herpes simplex virus in immunocompetent patients have been generally ineffective. We investigated whether in vitro drug measures could predict in vivo efficacy. Twelve topical antiviral formulations were evaluated in vitro by measuring inhibition of viral plaque formation in cell culture (ID50) and drug penetration through excised guinea pig skin. In vivo efficacy for each treatment was determined in an experimental cutaneous infection with herpes simplex virus type 1 in guinea pigs and expressed as the percent reduction in lesion number, lesion area, and virus titer in the lesions. The in vitro findings were correlated with the results in the animal model. ID50 was a poor predictor of in vivo efficacy, whereas stronger correlations were found between the degree of skin penetration and in vivo activity. The best correlation was noted by using a summary expression of the in vitro results as follows: the ratio of drug penetration through skin at 37 C to ID50 (r = .95, .94, and .92 for lesion number, area, and virus titer, respectively, P less than .0005). Determination of this in vitro index should be included in the preclinical evaluation of new topical antiviral formulations.

    Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Diffusion; Female; Guinea Pigs; Herpes Simplex; Idoxuridine; Pharmaceutical Vehicles; Skin Diseases; Trifluridine; Vidarabine

1986
High-performance liquid chromatographic analysis of (E)-5-(2-bromovinyl)-2'-deoxyuridine and its metabolites in serum, urine and herpes simplex virus type-1 infected cells.
    Journal of chromatography, 1986, Mar-07, Volume: 375, Issue:2

    Topics: Animals; Bromodeoxyuridine; Cells, Cultured; Chlorocebus aethiops; Chromatography, High Pressure Liquid; Herpes Simplex; Humans; Indicators and Reagents

1986
Improvement of the bioavailability of the anti-herpes virus agent BVDU by use of 5'-O-alkoxycarbonyl derivatives with increased metabolic stability.
    The Journal of antimicrobial chemotherapy, 1986, Volume: 18 Suppl B

    (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was found by HPLC analysis to be rapidly metabolized in mice and in liver homogenates from mouse and man to the antivirally inactive (E)-5-(2-bromovinyl) uracil (BVU) but was comparatively stable in blood from both species. Of a series of 5'-O-alkoxycarbonyl derivatives of BVDU, the 5'-O-tert.-butoxycarbonyl derivative (BRL 37000) was the most stable in mouse and human blood and liver homogenates, neither its ester bond nor its N-glycosidic linkage being readily cleaved enzymically. Oral administration of BRL 37000 and the 5'-O-ethoxycarbonyl derivative (BRL 36101) to mice gave prolonged serum concentrations of BVDU and delayed the appearance of BVU compared with the BVDU control. BRL 36101 was more active than BVDU when administered orally to mice infected cutaneously with herpes simplex virus type 1.

    Topics: Animals; Antiviral Agents; Biological Availability; Bromodeoxyuridine; Herpes Simplex; Humans; In Vitro Techniques; Inactivation, Metabolic; Liver; Metabolic Clearance Rate; Mice; Structure-Activity Relationship

1986
5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analogue.
    Journal of medicinal chemistry, 1985, Volume: 28, Issue:11

    Syntheses of 5-(2-haloethyl)-2'-deoxyuridines, 5-(3-chloropropyl)-2'-deoxyuridines, and 5-(2-chloroethyl)-2'-deoxycytidine are described. The antiviral activities of these compounds were determined in cell culture against herpes simplex virus types 1 and 2. All compounds were shown to possess significant and selective antiviral activity. The most potent derivative, 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), inhibited HSV-1 at concentrations below 0.1 microgram/mL. It exerted measurable inhibitory effects on cell proliferation only at concentrations higher than 100 micrograms/mL. In vivo CEDU reduced the mortality rate of HSV-1-infected mice at concentrations lower than 5 mg/kg per day when given intraperitoneally and orally. Thus, it proved to be more effective in this in vivo model than the reference compounds (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)methyl]guanine (ACV).

    Topics: Animals; Bromodeoxyuridine; Chemical Phenomena; Chemistry; Deoxyuridine; Dose-Response Relationship, Drug; Halogens; Herpes Simplex; Mice; Rats

1985
Synthesis and antiviral activity of the carbocyclic analogues of (E)-5-(2-halovinyl)-2'-deoxyuridines and (E)-5-(2-halovinyl)-2'-deoxycytidines.
    Journal of medicinal chemistry, 1985, Volume: 28, Issue:5

    The carbocyclic analogues of the potent and selective antiherpes agents (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC) were synthesized by conventional methods with use of carbocyclic 2'-deoxyuridine as starting material. C-BVDU, C-IVDU, and C-BVDC were equally selective, albeit slightly less potent, in their antiherpes action than BVDU, IVDU, and BVDC. Although resistant to degradation by pyrimidine nucleoside phosphorylases, C-BVDU did not prove more effective than BVDU in the systemic (oral, intraperitoneal) or topical treatment of HSV-1 infections in mice.

    Topics: Animals; Antineoplastic Agents; Antiviral Agents; Bromodeoxyuridine; Cell Division; Cell Line; Cyclopentanes; Cytopathogenic Effect, Viral; Deoxycytidine; Deoxyuridine; Herpes Simplex; Humans; Mice; Mice, Hairless; Rabbits; Rats; Simplexvirus; Vaccinia virus; Vesicular stomatitis Indiana virus; Virus Cultivation

1985
Preclinical assessment of topical treatments of herpes simplex virus infection: 5% (E)-5-(2-bromovinyl)-2'-deoxyuridine cream.
    Antiviral research, 1985, Volume: 5, Issue:3

    The potential efficacy of topical therapy with (E)-5-w-bromovinyl)-2'-deoxyuridine (BVDU) for cutaneous herpesvirus infection was evaluated in vitro and in guinea pigs. Drug sensitivity testing against herpes simplex virus type 1 strain E115 revealed an ID50 of 0.008 microgram/ml for BVDU and 0.19 microgram/ml for acyclovir (ACV). In vitro drug diffusion studies showed poor penetration of guinea pig skin by BVDU from the cream compared to BVDU from dimethylsulfoxide (DMSO) (0.04 vs. 1.5 microgram/cm2 per h). 5% BVDU cream, 5% BVDU/DMSO, and 5% ACV in polyethylene glycol (PEG) were then compared in the treatment of experimental dorsal cutaneous HSV-1 infection in guinea pigs. Lesion number, total lesion area and virus titer were reduced by all three formulations compared to control sites treated with the corresponding drug vehicles (P less than or equal to 0.01). BVDU cream effected a greater reduction in lesion number (20+ vs. 13%) and total lesion area (40% vs. 28%) than did ACV/PEG and a significantly greater decrease in virus titer (990% vs. 55%, P less than 0.002). BVDU/DMSO was clinically twice as effective as BVDU cream (P less than or equal to 0.01) and reduced lesion virus titers to a similar degree. The results of these studies show that BVDU is a more potent virus-inhibitory agent than ACV in vitro and is superior to topical ACV in vivo when formulated in a simple aqueous cream. The marked efficacy of BVDU/DMSO in the animal model demonstrates the potential of this antiviral if drug delivery is improved.

    Topics: Absorption; Acyclovir; Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Dimethyl Sulfoxide; Female; Guinea Pigs; Herpes Simplex; Polyethylene Glycols; Simplexvirus; Skin; Viral Plaque Assay

1985
Lack of oral HSV-2 in a college student population.
    Journal of medical virology, 1985, Volume: 16, Issue:3

    A population of individuals with a high incidence of genital herpes simplex virus type 1 (HSV-1), due most likely to oro-genital contact, was examined to determine the incidence of oral herpes simplex virus type 2 (HSV-2) infection. Herpes simplex virus was isolated from the oral cavity of 43 college students whose symptoms ranged from singular lesions of the lips with minimal discomfort to severe oral disease with systemic involvement resulting in lymphadenopathy, chills, sweat, myalgia, and fever. The virus isolated from each case was identified by serum neutralization and typed as HSV-1 or HSV-2 using (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA. In every instance the isolate was HSV-1. Additional identification and typing of head and neck isolates as well as oral samples from non-university patients demonstrated that all were also HSV-1. Therefore, while HSV-1 appears to be readily transmitted to the genitalia in this group of individuals, the transmission of HSV-2 to the oral cavity may not be as common, even though clinical histories revealed that several of these patients were engaging in oro-genital contact.

    Topics: Adult; Antibodies, Monoclonal; Antibodies, Viral; Bromodeoxyuridine; DNA, Viral; Face; Female; Herpes Labialis; Herpes Simplex; Humans; Male; Mouth; Sexual Behavior; Simplexvirus; Students; Virus Replication

1985
HSV1-specific thymidylate kinase activity in infected cells.
    Intervirology, 1985, Volume: 24, Issue:1

    Several 5-methoxymethyldeoxyuridine (MMdU)-resistant mutants of herpes simplex virus type 1 (HSV1) were classified by measuring their sensitivities to the deoxythymidine kinase (dTK)-dependent antiviral drugs 9-(2-hydroxyethoxymethyl)-guanine (acyclovir, ACV), 1-beta-D-arabinofuranosylthymine (araT), and E-(2)-5-bromovinyldeoxyuridine (BVdU) and to the dTK-independent antiviral drug phosphonoacetate (PAA). Compared to wild-type (WT) virus, all five of the dTK- mutants were highly resistant (greater than or equal to 500-fold) to BVdU and MMdU, moderately resistant to ACV (50- to 100-fold) and araT (10- to 20-fold), but not resistant to PAA. The dTK of the mutant MMdUr-20 (dTK+) appeared to phosphorylate dTMP less well than that of the WT virus, while its affinity for deoxythymidine was not altered. Two other drug-resistant HSV mutants-S1 (isolated against ACV) and B3 (isolated against BVdU)--also showed reduced phosphorylation of dTMP. This suggests that alterations in both dTK and thymidylate kinase activities may determine sensitivity to antiviral drugs.

    Topics: Acyclovir; Animals; Bromodeoxyuridine; Cells, Cultured; Cricetinae; Deoxyuridine; Drug Resistance, Microbial; Herpes Simplex; Kinetics; Mice; Nucleoside-Phosphate Kinase; Phosphonoacetic Acid; Phosphorylation; Phosphotransferases; Substrate Specificity

1985
Comparison of immunofluorescence with commercial monoclonal antibodies to biochemical and biological techniques for typing clinical herpes simplex virus isolates.
    Journal of clinical microbiology, 1985, Volume: 22, Issue:5

    Immunofluorescence with monoclonal antibody reagents from two commercial sources for differentiating herpes simplex viruses types 1 and 2 demonstrated 100% agreement with cell culture selectivity (chicken embryo and guinea pig embryo cells) and (E)-5-(2-bromovinyl)-2'-deoxyuridine sensitivity for typing a total of 94 clinical herpes simplex virus isolates.

    Topics: Antibodies, Monoclonal; Bromodeoxyuridine; Cells, Cultured; Fluorescent Antibody Technique; Herpes Simplex; Humans; Microbial Sensitivity Tests; Serotyping; Simplexvirus

1985
[Antiviral therapy of immunocompromised patients].
    Immunitat und Infektion, 1984, Volume: 12, Issue:4

    For immunocompromised patients virus infections represent a definite risk, particularly infections with measles virus and viruses of the herpes group (primary infections or reactivations). Vidarabine, acyclovir and bromovinyldeoxyuridine are therapeutically active against varicella, zoster, and herpes simplex, provided they are administered early in the course of disease. For zoster at least, the efficacy of interferon has been documented in controlled studies. No convincing therapy is so far available for the severe cytomegalovirus infections. Interferons obtained with DNA recombinant techniques are of significant promise in the near future.

    Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immune System Diseases; Vidarabine; Virus Diseases

1984
Metabolic fate of (E)-5-(2-bromovinyl)-2'-deoxyuridine in herpes simplex virus- and mock-infected cells.
    Antimicrobial agents and chemotherapy, 1984, Volume: 26, Issue:5

    (E)-5-(2-Bromovinyl)-2'-deoxyuridine is a potent antiherpes compound with far better activity against herpes simplex virus type 1 than type 2. To understand the role of drug metabolism in this differential antiviral activity, we examined the metabolic fate of this drug in virus-infected and mock-infected Vero cells by high-pressure liquid chromatography. After 8 h of incubation in which cells were exposed to 10 micrograms of the drug per ml, 63 pmol/10(6) cells of the parent compound was detected in acid-soluble extracts of mock-infected cells. Herpes simplex virus-infected cells, however, incorporated or metabolized, or both, up to 11,310 pmol/10(6) cells. Type 1-infected cells metabolized the drug to the triphosphate where as many as 5,565 pmol/10(6) cells were detected. In contrast, three strains of type 2-infected cells metabolized the drug to the monophosphorylated nucleotide and no further. The amount of drug getting into the cells was virus strain and inoculum dependent. These studies indicate that poor substrate acceptance of (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate by herpes simplex virus type 2-specified thymidylate kinase is an important factor in situ in infected cells, preventing anabolism of the parent compound to its active triphosphorylated form. This may account for its type specificity.

    Topics: Antiviral Agents; Bromodeoxyuridine; Cell Line; Chromatography, High Pressure Liquid; Herpes Simplex; Humans; Kinetics; Simplexvirus

1984
Antiherpes activity of some novel analogues of (E)-5-(2-bromovinyl)-2'-deoxyuridine (E-BrVUdR) in two different cell lines.
    Acta virologica, 1984, Volume: 28, Issue:1

    In a series of 5-vinyl-2'-deoxyuridine (VUdR) analogues (5-(2-X-vinyl)-UdRs) the (E)-5-(2-bromovinyl)-UdR (E-BrVUdR) proved the most potent inhibitor of plaque formation of two herpes simplex virus type 1 (HSV-1) strains in human embryonic lung fibroblast (HELF) and African green monkey kidney (Vero) cell cultures. The (Z)-5-(2-bromovinyl)-UdR (Z-BrVUdR) isomer and the 5-(2,2-dibromovinyl)-UdR (Br2VUdR) analogue were 10-20 times less efficient, whereas the (E)-5-(2-cyanovinyl)-UdR (CNVUdR) and the (E)-5-(2-carboxyvinyl)-UdR (COOHVUdR) derivative were only marginally active (10(3)-10(4) times less than E-BrVUdR). The antiherpes potential of the 5-(2-X-vinyl)-UdRs was compared with that of 5-iodo-, 5-fluoro-, 5-formyl- and 5-ethyl-UdR (IUdR, FUdR, fUdR, EUdR) as well as of 9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACV), 2'-fluoro-5-iodo-1-beta-D-arabinofuranosyl(ara)-cytosine (FIAC), 2'-fluoro-5-methylarauracil (FMAU), arabinosylthymine (araT) and (E)-5-(2-bromovinyl)- and 5-vinyl-araU (BrVaraU, VaraU). In HELF cells the following order of decreasing activity against HSV-1-77 was found: E-BrVUdR greater than greater than BrVaraU greater than VaraU greater than FIAC greater than FMAU = VUdR = = Z-BrVUdR = ACV = araT = FUdR greater than Br2VUdR greater than greater than IUdR greater than fUdR greater than EUdR greater than CNVUdR greater than COOHVUdR. The inhibition of HSV-1 replication by most of the investigated compounds was somewhat weaker in the plaque inhibition assay on Vero than on HELF cells, but, in the case of the 5-X-araU reference compounds the activity was strongly reduced in Vero cells. In HELF cells the order of decreasing potential against HSV-2 strain 42/78 (HSV-2-42/78) was: FIAC = FMAU greater than greater than araT greater than IUdR = VUdR greater than ACV = FUdR = greater than fUdR = EUdR = VaraU greater than E-BrVUdR greater than Z-BrVUdR greater than Br2VUdR greater than greater than BrVaraU; CNVUdR and COOHVUdR were nearly inactive.

    Topics: Antiviral Agents; Bromodeoxyuridine; Cells, Cultured; Herpes Simplex; Humans; Simplexvirus; Structure-Activity Relationship; Virus Replication

1984
A quantitative study of the effects of several nucleoside analogues on established herpes encephalitis in mice.
    The Journal of general virology, 1984, Volume: 65 ( Pt 4)

    Mice with established herpes encephalitis were used to compare the effects of chemotherapy using three different nucleoside analogues. Encephalitis was produced by intranasal inoculation of a type 1 strain of herpes simplex virus. Without chemotherapy all mice died within 5 to 7 days of inoculation. Oral acyclovir (ACV) was a successful preventative measure if commenced within 2 days of inoculation but much less effective if the onset of treatment was further delayed. From the third day, when central nervous system infection had definitely become established, ACV only reduced mortality if given intraperitoneally (i.p.) at regular 6-hourly intervals. Comparison with bromovinyldeoxyuridine (BVdU) and the new nucleoside analogue dihydroxypropoxymethylguanine (DHPG) using the same 6-hourly i.p. regimen revealed that BVdU was poorly effective, despite better activity in vitro, whereas DHPG was the most successful. Virus was rapidly eradicated from all parts of the brain by DHPG therapy, and by day 10, no infectious virus remained in the brains of treated mice, no virus antigens were observed and no trace of virus DNA could be detected in neural tissues by Southern blotting.

    Topics: Acyclovir; Animals; Antiviral Agents; Brain; Bromodeoxyuridine; Encephalitis; Female; Ganciclovir; Herpes Simplex; Mice; Mice, Inbred BALB C; Simplexvirus; Time Factors; Trigeminal Ganglion; Virus Replication

1984
In vitro effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, 5'-amino-5-iodo-2',5'-dideoxyuridine and 2-deoxy-D-glucose on latent ganglionic herpes simplex virus infection.
    Antiviral research, 1984, Volume: 4, Issue:1-2

    (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU) and 5'-amino-5-iodo-2',5'-dideoxy-uridine AIdUrd, blocked the reactivation of latent ganglionic herpes simplex virus in vitro. Furthermore, BVDU, but not AIdUrd, blocked the multiplication of reactivated latent virus and transiently suppressed emergence of reactivated virus from the sensory ganglia after removal of drug from the medium. 2-Deoxy-D-glucose (2-DG) neither prevented the in vitro reactivation of latent virus nor blocked the further multiplication of reactivated latent virus.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Deoxy Sugars; Deoxyglucose; Herpes Simplex; Idoxuridine; Male; Mice; Mice, Inbred BALB C; Simplexvirus; Trigeminal Ganglion; Trigeminal Nerve; Virus Activation; Virus Replication

1984
Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections.
    Antiviral research, 1984, Volume: 4, Issue:5

    As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 keratitis and HSV-1 uveitis. BVDU 0.1% eye drops have also proven efficacious in the treatment of patients with dendritic corneal ulcers, geographic corneal ulcers and stromal keratitis, and combined treatment of BVDU 0.1% eye drops with oral BVDU at 375 mg/day for 5 days led to a prompt healing of keratouveitis and skin lesions in patients with ophthalmic herpes zoster.

    Topics: Animals; Bromodeoxyuridine; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Keratitis; Keratitis, Dendritic; Rabbits; Uveitis

1984
Topical treatment of cutaneous herpes simplex virus infection in hairless mice with (E)-5-(2-bromovinyl)-2'-deoxyuridine and related compounds.
    Antimicrobial agents and chemotherapy, 1984, Volume: 26, Issue:2

    (E)-5-(2-Bromovinyl)-2'-deoxyuridine (bromovinyldeoxyuridine) was found to suppress the development of herpetic skin lesions and the paralysis and mortality associated therewith in hairless mice inoculated intracutaneously with herpes simplex virus type 1. This protective effect was achieved with bromovinyldeoxyuridine applied topically at 1, 3, or 10% in either dimethylsulfoxide (DMSO), Beeler base, Tween-glycerol-water, 5% Azone (1-dodecylazacycloheptan-2-one) in water, or 5% Azone in DMSO. The optimal vehicle was 5% Azone in DMSO, in which bromovinyldeoxyuridine was effective even at a concentration as low as 0.3%. In its protective activity against cutaneous herpes simplex virus type 1 infection in hairless mice, bromovinyldeoxyuridine was clearly superior to other established antiherpes compounds such as 5-iodo-2'-deoxyuridine, 5-ethyl-2'-deoxyuridine, arabinosyl thymine, and arabinosyl (E)-5-(2-bromovinyl) uracil when formulated at 10% in DMSO or Azone-DMSO. However, no activity was noted with any of these drug formulations against cutaneous herpes simplex virus type 2 infection. In contrast, acycloguanosine (acyclovir) proved quite effective in the topical treatment of cutaneous herpes simplex virus type 2 infection when used at 10% in DMSO or at 5% in propylene glycol.

    Topics: Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Dimethyl Sulfoxide; Herpes Simplex; Mice; Mice, Hairless; Pharmaceutical Vehicles

1984
Synthesis of 131I, 125I and 82Br labelled (E)-5-(2-halovinyl)-2'-deoxyuridines.
    The International journal of applied radiation and isotopes, 1984, Volume: 35, Issue:11

    Radiohalogenated (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU, 4) and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, 5) were synthesized by reaction of (E)-5-(2-carboxyvinyl)-2'-deoxyuridine (1) with radiolabelled iodide or bromide in the presence of chloramine-T. A "no-carrier-added" synthesis of [131I]IVDU was completed within 30 min providing a radiochemical yield of 65%. Alternatively, radioactive iodine was incorporated into IVDU using a halogen isotope exchange reaction catalyzed by cuprous ion. [82Br]BVDU was also prepared by direct neutron activation of unlabelled BVDU.

    Topics: Antiviral Agents; Bromine; Bromodeoxyuridine; Encephalitis; Herpes Simplex; Humans; Idoxuridine; Iodine Radioisotopes; Isotope Labeling; Radioisotopes; Radionuclide Imaging

1984
Current aspects of anti-herpes research: problem, established work, and future goals.
    CDA journal, 1984, Volume: 12, Issue:12

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Herpes Simplex; Humans; Recurrence

1984
Structural requirements of olefinic 5-substituted deoxyuridines for antiherpes activity.
    Journal of medicinal chemistry, 1983, Volume: 26, Issue:9

    A number of structurally related 5-substituted pyrimidine 2'-deoxyribonucleosides were synthesized and tested for antiviral activity against herpes simplex virus type 1 (HSV-1) in cell culture. A minimum inhibitory concentration was determined for each compound, and from a comparison of these values a number of conclusions were drawn with regard to those molecular features that enhance or reduce antiviral activity. Optimum inhibition of HSV-1 in cell culture occurred when the 5-substituent was unsaturated and conjugated with the pyrimidine ring, was not longer than four carbon atoms in length, had E stereochemistry, and included a hydrophobic, electronegative function but did not contain a branching point. Such features are contained in (E)-5-(2-bromovinyl)-2'-deoxyuridine, which was the most active of the compounds described.

    Topics: Animals; Cricetinae; Deoxyuridine; Herpes Simplex; Stereoisomerism; Structure-Activity Relationship

1983
Efficacy of (E)-5-(2-bromovinyl)-2'-deoxyuridine in the treatment of experimental herpes simplex virus encephalitis in mice.
    Antiviral research, 1983, Volume: 3, Issue:1

    Systemic treatment of mice with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) showed a significant therapeutic efficacy against herpes simplex type 1 virus (HSV-1) encephalitis. With treatment initiated 12 h after viral inoculation and continued for 10 consecutive days, BVDU administered intraperitoneally in daily doses of 100-500 mg/kg increased the 21-day survival rates from 30 to 100% and reduced brain virus titers by 3-4 log10 on day 6 post-infection. Furthermore, at doses of 300-500 mg/kg per day BVDU prevented the establishment of latent virus infection in the trigeminal ganglia following intracerebral HSV-1 inoculation.

    Topics: Animals; Antiviral Agents; Brain; Bromodeoxyuridine; Encephalitis; Ganglia; Herpes Simplex; Male; Mice; Virus Replication

1983
High efficiency latency and activation of herpes simplex virus in human cells.
    Science (New York, N.Y.), 1982, Sep-17, Volume: 217, Issue:4565

    Herpes simplex virus (HSV) exists in humans in a latent form that can be activated. To characterize the molecular basis of the cell-virus interactions and to analyze the state of the latent HSV genome, an in vitro model system was established. In this system a large fraction of the latently infected cells contain an HSV genome that can be activated. Cell survival was reduced minimally after repression of high multiplicity HSV type 1 (HSV-1) infection of human fibroblast cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine in combination with human leukocyte interferon (IFN-alpha). A minimum of 1 to 3 percent of the surviving cells contained an HSV genome that could be activated either by human cytomegalovirus superinfection or reduction in incubation temperature.

    Topics: Bromodeoxyuridine; Cells, Cultured; Cytarabine; Herpes Simplex; Humans; Interferons; Simplexvirus; Virus Activation; Virus Replication

1982
Isolation of bromovinyldeoxyuridine-resistant strains of herpes simplex virus and successful chemotherapy of mice infected with one such strain by using acyclovir.
    Antiviral research, 1982, Volume: 2, Issue:5

    Several strains of herpes simplex virus which were resistant to bromovinyldeoxyuridine were isolated by passaging the virus in the presence of the drug in tissue culture. The resistance of the majority of isolates was accounted for by their reduced ability to induce the enzyme thymidine kinase. These strains were co-resistant to acyclovir, but showed reduced pathogenicity in mice. However, another type of bromovinyldeoxyuridine-resistant virus was isolated which induced normal levels of thymidine kinase and retained virulence for mice. This resistant virus was sensitive to acyclovir and was successfully treated using oral acyclovir therapy.

    Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Drug Resistance, Microbial; Herpes Simplex; Mice; Mice, Inbred BALB C; Simplexvirus; Thymidine Kinase; Virulence

1982
Efficacy of (E)-5-(2-bromovinyl)-2'-deoxyuridine against different herpes simplex virus strains in cell culture and against experimental herpes encephalitis in mice.
    Antiviral research, 1982, Volume: 2, Issue:5

    (E)-5-(2-Bromovinyl-2'-deoxyuridine (BrVUdR) showed strong antiviral activity against different laboratory strains and clinical isolates of herpes simplex virus type 1 (HSV-1) on primary rabbit testes (PRT) cells with a 50% inhibition of plaque formation (ID50) at 0.01-0.02 microM. One laboratory strain (HSV-1-S), however, was completely refractory even at concentrations as high as 100 microM. In contrast, the ID50S for all herpes simplex virus type 2 (HSV-2) strains were about 10(2) - 10(3) times higher (8-25 microM) than for the HSV-1 strains. No toxicity in mice treated with 140 mg BrVUdR/kg/day for 14 days was observed, and successful treatments of herpes encephalitis in mice induced experimentally by intracerebral infection with one laboratory strain (HSV-1-Kupka) and one clinical isolate (HSV-1-64) were achieved. Treatment of encephalitis in mice induced by the strain HSV-1-S insensitive to BrVUdR in cell culture failed to be effective. Similar antibody titers against HSV-1 were found in surviving mice of the control and of the BrVUdR-treated groups.

    Topics: Animals; Antibodies, Viral; Bromodeoxyuridine; Cells, Cultured; Encephalitis; Female; Herpes Simplex; Male; Mice; Rabbits; Rats; Simplexvirus; Testis; Viral Plaque Assay

1982
Chemotherapeutic efficacy of E-5-(2-bromovinyl)-2'deoxyuridine for orofacial infection with herpes simplex virus type 1 in mice.
    The Journal of infectious diseases, 1982, Volume: 145, Issue:6

    Systemic or topical treatment with E-5-(2-bromovinyl)2'-deoxyuridine (BVDU) showed significant efficacy against orofacial infection with herpes simplex virus type 1 (HSV-1) in hairless mice. The chemotherapeutic response to BVDU was dose-dependent and clearly evident even when the treatment was initiated during the clinical manifestation of HSV-1 infection at 72 hr after inoculation. Early initiation of therapy with BVDU at 3 or 24 hr after inoculation significantly prevented the establishment of latent HSV infection in the trigeminal ganglia of mice, but systemic treatment with BVDU did not influence already established latent HSV-1. The chemotherapeutic efficacy of BVDU was comparable to that of acyclovir in the present animal model.

    Topics: Acyclovir; Administration, Topical; Animals; Bromodeoxyuridine; Face; Guanine; Herpes Labialis; Herpes Simplex; Male; Mice; Mice, Inbred BALB C; Skin Diseases, Infectious; Time Factors; Trigeminal Ganglion

1982
Differential effects of E-5-(2-bromovinyl)-2'-deoxyuridine on infections with herpes simplex virus type 1 and type 2 in hairless mice.
    The Journal of infectious diseases, 1982, Volume: 145, Issue:1

    Topics: Animals; Bromodeoxyuridine; Herpes Simplex; Mice; Mice, Nude

1982
Treatment of experimental herpes simplex virus encephalitis with (E)-5-(2-bromovinyl)-2'-deoxyuridine in mice.
    Antimicrobial agents and chemotherapy, 1982, Volume: 22, Issue:3

    (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU) was examined for its ability to increase the survival rate of mice infected intracerebrally with herpes simplex virus type 1 (strain KOS). BVDU was administered orally (through the drinking water), intraperitoneally, or subcutaneously at doses ranging from 40 to 400 mg/kg per day, starting 0, 2, 4, or 6 days postinfection. Regardless of the route of administration, BVDU effected a significant reduction in the mortality rate of mice infected with herpes simplex virus type 1 if treatment was initiated shortly after virus infection, i.e., day 0 or 2 (or day 4, if BVDU was administered subcutaneously) postinfection, at a dosage of 80 mg/kg per day or higher. Similar beneficial effects were noted with orally administered BVDU in mice inoculated intraperitoneally or intranasally with herpes simplex virus type 1. These findings establish the therapeutic efficacy of BVDU in the systemic treatment of herpes simplex virus type 1 encephalitis in mice.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Encephalitis; Herpes Simplex; Mice

1982
E-5-(2-bromovinyl)-2'-deoxyuridine vs. interferon in the systemic treatment of infection with herpes simplex virus of athymic nude mice.
    The Journal of infectious diseases, 1981, Volume: 143, Issue:6

    The effects of systemic administration of E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and interferon (IFN)--mouse IFN type I (MuIFN-alpha plus -beta), mouse IFN type II (MuIFN-gamma), and polyriboinosinic-polyribocytidylic acid (an IFN inducer)--on the development of herpetic skin lesions and associated mortality were studied in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus (HSV) type 1 (strain KOS). BVDU was given intraperitoneally or orally at dosages of up to 5 mg per mouse per day; IFN and polyriboinosinic-polyribocytidylic acid were given intraperitoneally at dosages of up to 10(6) units per mouse per day and 100 microgram per mouse per day, respectively. Under conditions in which BVDU effectively suppressed the progression of the disease, IFN and polyriboinosinic-polyribocytidylic acid failed to suppress the disease. Thus, BVDU was superior to IFN in the treatment of HSV infection in immunologically compromised mice.

    Topics: Animals; Bromodeoxyuridine; Dose-Response Relationship, Drug; Herpes Simplex; Interferons; Mice; Mice, Nude; Poly I-C; Time Factors

1981
Effects of oral treatment with acyclovir and bromovinyldeoxyuridine on the establishment of maintenance of latent herpes simplex virus infection in mice.
    The Journal of general virology, 1981, Volume: 56, Issue:Pt 2

    Mice infected with herpes simplex virus (HSV) were treated (separately) with the nucleoside analogues acyclovir or bromovinyldeoxyuridine by incorporating the drugs in the drinking water. This method of treatment was found to be effective for both drugs and compared favourably with intraperitoneal injection. Prompt treatment with either compound could prevent the establishment of latent infections but latent infections once established were intractable using prolonged courses of oral administration.

    Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Bromodeoxyuridine; Ganglia; Guanine; Herpes Simplex; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Simplexvirus; Time Factors

1981