Novel inhibitors of HSV-1 protease effective in vitro and in vivo
Abstract
Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy.
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BibTeX
@article{pachota2026novel,
title = {{Novel inhibitors of HSV-1 protease effective in vitro and in vivo}},
author = {Magdalena Pachota and Renata Grzywa and Jakub Iwanejko and Aleksandra Synowiec and Dominika Iwan and Karolina Kamińska and Marcin Skoreński and Ewa Bielecka and Krzysztof Szczubiałka and Maria Nowakowska and Cameron D Mackereth and Elżbieta Wojaczyńska and Marcin Sieńczyk and Krzysztof Pyrć},
journal = {Antiviral Research},
year = {2026},
month = oct,
doi = {10.1016/j.antiviral.2023.105604},
url = {https://hal.science/hal-05824613v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Novel inhibitors of HSV-1 protease effective in vitro and in vivo
AU - Magdalena Pachota
AU - Renata Grzywa
AU - Jakub Iwanejko
AU - Aleksandra Synowiec
AU - Dominika Iwan
AU - Karolina Kamińska
AU - Marcin Skoreński
AU - Ewa Bielecka
AU - Krzysztof Szczubiałka
AU - Maria Nowakowska
AU - Cameron D Mackereth
AU - Elżbieta Wojaczyńska
AU - Marcin Sieńczyk
AU - Krzysztof Pyrć
PY - 2026
DA - 2026/10/20
JO - Antiviral Research
DO - 10.1016/j.antiviral.2023.105604
UR - https://hal.science/hal-05824613v1
AB - Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy.
SN - 0166-3542
ER -