What question did this study set out to answer?

To determine whether novel thymidine analogs exert their antiviral activity through selective phosphorylation by orthopoxvirus thymidine kinase relative to human cellular thymidine kinase.

February 27, 2007Antimicrobial Agents and ChemotherapyOpen Access

Selective Phosphorylation of Antiviral Drugs by Vaccinia Virus Thymidine Kinase

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Authors

MPMark N. PrichardUniversity of Alabama at Birmingham KKKathy A. KeithUniversity of Alabama at Birmingham MJMary P. Johnson

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Implication

In vitro study reveals selective phosphorylation of thymidine analogs by poxvirus thymidine kinase, suggesting a strategy for designing targeted orthopoxvirus inhibitors.

Key Points

To determine whether novel thymidine analogs exert their antiviral activity through selective phosphorylation by orthopoxvirus thymidine kinase relative to human cellular thymidine kinase.
Evaluated antiviral activities of novel 5-substituted deoxyuridine and thymidine analogs against wild-type and thymidine kinase-deficient strains of vaccinia virus, cowpox virus, herpes simplex virus, and varicella-zoster virus.
Expressed recombinant vaccinia virus thymidine kinase and human thymidine kinase 1 (TK1) in bacteria, purified the enzymes, and conducted comparative enzymatic phosphorylation assays.
Multiple thymidine analogs demonstrated potent antiviral activity against wild-type viruses but exhibited substantially reduced efficacy against thymidine kinase-deficient cowpox virus strains.
Purified vaccinia virus thymidine kinase efficiently phosphorylated the novel analogs, whereas the compounds served as very poor substrates for cellular human TK1.

Cite This Study

Prichard et al. (2007) studied this question.

synapsesocial.com/papers/6a9824dc824c98cfb78bfe5e https://doi.org/10.1128/aac.01447-06

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Implication

In vitro study reveals selective phosphorylation of thymidine analogs by poxvirus thymidine kinase, suggesting a strategy for designing targeted orthopoxvirus inhibitors.

Selective Phosphorylation of Antiviral Drugs by Vaccinia Virus Thymidine Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

Selective Phosphorylation of Antiviral Drugs by Vaccinia Virus Thymidine Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

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