Helicase-Primase as a Target of New Therapies for Herpes Simplex Virus Infections

The seminal discovery of acyclovir 40 years ago heralded the modern era of truly selective antiviral therapies and this drug remains the therapy of choice for herpes simplex virus infections. Yet by modern standards, its antiviral activity is modest and new drugs against novel molecular targets such...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2015-01, Vol.97 (1), p.66-78
Main Authors: James, SH, Larson, KB, Acosta, EP, Prichard, MN
Format: Article
Language:English
Subjects:
Acyclovir - pharmacology
Acyclovir - therapeutic use
Animals
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
DNA Helicases - antagonists & inhibitors
DNA Primase - antagonists & inhibitors
Drug Design
Drug Resistance, Viral
Herpes Simplex - drug therapy
Herpes Simplex - virology
Humans
Molecular Targeted Therapy
Oxadiazoles - pharmacology
Oxadiazoles - therapeutic use
Pyridines - pharmacology
Pyridines - therapeutic use
Thiazoles - pharmacology
Thiazoles - therapeutic use
Viral Proteins - antagonists & inhibitors
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Summary:The seminal discovery of acyclovir 40 years ago heralded the modern era of truly selective antiviral therapies and this drug remains the therapy of choice for herpes simplex virus infections. Yet by modern standards, its antiviral activity is modest and new drugs against novel molecular targets such as the helicase‐primase have the potential to improve clinical outcome, particularly in high‐risk patients. A brief synopsis of current therapies for these infections and clinical need is provided to help provide an initial perspective. The function of the helicase‐primase complex is then summarized and the development of new inhibitors of the helicase‐primase complex, such as pritelivir and amenamevir, is discussed. We review their mechanism of action, propensity for drug resistance, and pharmacokinetic characteristics and discuss their potential to advance current therapeutic options. Strategies that include combinations of these inhibitors with acyclovir are also considered, as they will likely maximize clinical efficacy.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.3