Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with acyclovir-resistant herpes simplex-virus is now a clinical reality in patients with AIDS or who are otherwise immunocompromised. The most common mechanism of resistance is selection of mutants with inability to express thymidine kinase activity. Vidarabine, foscarnet and gancyclovir can be used to treat infections with acyclovir resistant virus. In recent years there have been many reports of drug resistance from the treatment of other virus infections too.
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PMID:[Acyclovir-resistant herpes simplex virus]. 217 Nov 55

Sensitivity of Herpes Simplex Virus type I (HSV-I) mutants carrying genetic defect in the DNA polymerase and thymidine kinase genes to the action of some drugs was studied. TK- mutant of HSV-I was resistant to Ara-T and ACG and sensitive to PAA, Ara-A as well as to ribavirin and ADEA. PAAr mutant of HSV-I was resistant to PAA, Ara-A, ACG and sensitive to Ara-T, ribavirin and ADEA. A double mutant of HSV-I-TK-, PAAr was resistant to all drugs, except for ribavirin and ADEA. To inhibit reproduction of HSV with genetic defect, it is important using drugs of independent mode of action on the function of defective viral gene.
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PMID:[Inhibition of the reproduction of a herpes simplex I virus carrying mutations in the thymidine kinase and DNA polymerase genes]. 301 23

The effects of repeated topical idoxuridine (IDU) administration of HSV1 strain sensitivity were investigated during 6 serial passages (P1 to P6) in the rabbit. By comparison to placebo treated rabbits, a delay in ulcer cicatrization appeared at P2 and clinical resistance was completed at P3. Clinical cross resistance to acyclovir (ACV) was also tested and demonstrated at P7. In vitro, a plaque reduction test on Vero cells using directly the tear film HSV populations allowed the prediction of the resistance by an early rise in the effective dose 90% (ED 90) value anticipating that in ED 50%. An ED 50 determination by dye-uptake assay on P6 HSV isolate demonstrated a cross resistance to viral thymidine kinase (TK) dependent drugs without any change in Ara-A and PFA sensitivity, according to a 23% TK activity at P6. At the last passage the HSV drug resistant population had an unrestricted corneal pathogenicity. A return to IDU and ACV in vitro sensitivity was demonstrated in group control animals at P2 but not at P4 or P6.
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PMID:HSV1 strain sensitivity in experimental rabbit keratitis: evolution under repeated topical IDU administrations. 303 Jun 53

Vidarabine (9-beta-D-arabinofuranosyladenine) prepared in a 70% dimethyl sulfoxide vehicle was applied topically to type 1 herpesvirus-induced cutaneous lesions on guinea pigs and athymic nude mice. Treatments were 3 or 5 times daily for 7 days beginning 24 h after virus exposure. Against infections in guinea pigs induced by a thymidine kinase-positive virus strain, either treatment schedule effectively inhibited mean lesion score, lesion size, appearance of new lesions, and reduced lesion virus titers. Therapy was similarly effective against infections in guinea pigs induced by a thymidine kinase-negative virus strain, except that lesion virus titers were somewhat increased in animals treated 3 times daily. Treatment 5 times daily was most efficacious against both virus strains. Treatment 3 times daily of mice infected with a thymidine kinase-negative virus was not effective, but treatment 5 times daily significantly inhibited lesion score and size and reduced lesion virus titer by 37%. Toxicity controls exhibited no signs of skin irritation, although guinea pigs treated 5 times daily experienced some transient weight loss.
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PMID:Effect of vidarabine in dimethyl sulfoxide vehicle on type 1 herpesvirus-induced cutaneous lesions in laboratory animals. 303 26

The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia.
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PMID:Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia. 620 91