Limitations of acyclovir and identification of potent HSV antivirals using 3D bioprinted human skin equivalents.

ABSTRACT: Herpes simplex virus (HSV) infection poses global public health concerns with lifelong impacts. Acyclovir, the standard therapy, has limited efficacy in preventing subclinical shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. Here we show that acyclovir is significantly less effective in skin-derived keratinocytes than donor-matched fibroblasts. Using 3D bioprinted human skin equivalents (HSEs) in a 96-well plate format, we have screened 738 compounds with broad targets and mechanisms of action, identifying potent antivirals, including 23 known or experimental HSV treatments. Unlike acyclovir, antivirals against HSV helicase/primase or host replication pathways display similar potency across cell types and donor sources in bot

SUBMITTER: Ellison ST 

PROVIDER: S-EPMC12533247 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature