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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Recent advances in the medicinal chemistry of HSV-1 inhibitors (2020-2025): Emerging targets, modalities, and
Qiaomei Zhou1, Baohu Li2, Yehong Dai2
1Department of Medicinal Chemistry, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, Shandong Basic Science Special Academic Zone (Pharmacy), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, PR China.
Abstract:
Herpes simplex virus type 1 (HSV-1) causes widespread human infection, for which curative therapies remain unavailable. First-line TK-dependent nucleoside analogues such as acyclovir fail to eradicate latent virus and show limited activity against drug-resistant variants, highlighting an urgent unmet medical need. This review critically surveys HSV-1 inhibitor research published from 2020 to 2025, covering viral-targeted agents acting at entry, helicase-primase, metal-dependent processing enzymes and capsid-maturation steps, as well as host-directed candidates. We discuss structural foundations, mechanisms, structure-activity relationships, resistance risks and translational bottlenecks of representative compounds. Three priority directions for future anti-HSV-1 drug discovery are outlined: constructing inhibitors with high genetic-barrier against resistance, optimizing tissue-matched delivery for local or CNS indications, and advancing strategies targeting latent HSV-1 reservoirs.
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