Herpes Simplex Viruses

Birkmann, Alexander

doi:10.1002/9783527810697.ch5

Cited by 1 publication

(1 citation statement)

References 86 publications

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“…Despite a continuous drive to address these shortcomings, no major breakthroughs have been achieved in HSV treatment since introduction of (val)acyclovir. , This may in part be attributed to the continuing focus on acyclovir’s target, the viral DNA polymerase. The only approved HSV drug to deviate from this approach is the long-chain alcohol, n -docosanol, which, while being an effective inhibitor of viral cell entry, is limited to topical administration on account of its very poor oral bioavailability…”

Section: Introductionmentioning

confidence: 99%

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

et al. 2022

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When the nucleoside analogue acyclovir was introduced in the early 1980s, it presented a game-changing treatment modality for herpes simplex virus infections. Since then, work has been ongoing to improve the weaknesses that have now been identified: a narrow time window for therapeutic success, resistance in immunocompromised patients, little influence on frequency of recurrences, relatively fast elimination, and poor bioavailability. The present Drug Annotation focuses on the helicase−primase inhibitor pritelivir currently in development for the treatment of acyclovir-resistant HSV infections and describes how a change of the molecular target (from viral DNA polymerase to the HSV helicase−primase complex) afforded improvement of the shortcomings of nucleoside analogs. Details are presented for the discovery process leading to the final drug candidate, the pivotal preclinical studies on mechanism of action and efficacy, and on how ongoing clinical research has been able to translate preclinical promises into clinical use.

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Section: Introductionmentioning

confidence: 99%