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Novel inhibitors of HSV-1 protease effective in vitro and in vivo.
- Source :
-
Antiviral Research . May2023, Vol. 213, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
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. [Display omitted] • A library of compounds was designed to target HSV-1 capsid protease. • Two compounds inhibited the protease, hindering virus replication. • VP24 protease inhibitors block viral capsid egress from the cell nucleus. • The compounds were effective against acyclovir-resistant HSV-1. • Protease inhibitors protected mice from lethal HSV-1 challenge. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HUMAN herpesvirus 1
*PROTEASE inhibitors
*CELL nuclei
*VIRAL encephalitis
Subjects
Details
- Language :
- English
- ISSN :
- 01663542
- Volume :
- 213
- Database :
- Academic Search Index
- Journal :
- Antiviral Research
- Publication Type :
- Academic Journal
- Accession number :
- 163259465
- Full Text :
- https://doi.org/10.1016/j.antiviral.2023.105604