A preclinical model for studying herpes simplex virus infection.

Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established a HSV-1 infection model on microneedle-pretreated human skin ex vivo. We identified HSV-1-specific histological changes (e.g. cytopathic effects, multinucleated giant cells), down regulation of nectin-1, nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB; p65), interferon regulatory factor 3 (IRF3), and signaling of the interferon-inducible protein MxA. Accordingly, this model was used to test the potency of pritelivir compared to the standard drug acyclovir. We discovered that both drugs had a comparable efficacy to inhibit HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research.