Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex

Abstract Herpesviruses infect a majority of the human population, establishing lifelong latent infections for which there is no cure. Periodic viral reactivation spreads infection to new hosts while causing various disease states particularly detrimental in the immunocompromised. Efficient viral rep...

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Autores principales:	Elizabeth B. Draganova, Ekaterina E. Heldwein
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5dc9c39447a54f43b26531225b79a2c5
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spelling	oai:doaj.org-article:5dc9c39447a54f43b26531225b79a2c52021-12-02T14:03:58ZVirus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex10.1038/s41598-021-83402-x2045-2322https://doaj.org/article/5dc9c39447a54f43b26531225b79a2c52021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83402-xhttps://doaj.org/toc/2045-2322Abstract Herpesviruses infect a majority of the human population, establishing lifelong latent infections for which there is no cure. Periodic viral reactivation spreads infection to new hosts while causing various disease states particularly detrimental in the immunocompromised. Efficient viral replication, and ultimately the spread of infection, is dependent on the nuclear egress complex (NEC), a conserved viral heterodimer that helps translocate viral capsids from the nucleus to the cytoplasm where they mature into infectious virions. Here, we have identified peptides, derived from the capsid protein UL25, that are capable of inhibiting the membrane-budding activity of the NEC from herpes simplex virus type 1 in vitro. We show that the inhibitory ability of the peptides depends on their length and the propensity to form an α-helix but not on the exact amino acid sequence. Current therapeutics that target viral DNA replication machinery are rendered ineffective by drug resistance due to viral mutations. Our results establish a basis for the development of an alternative class of inhibitors against nuclear egress, an essential step in herpesvirus replication, potentially expanding the current repertoire of available therapeutics.Elizabeth B. DraganovaEkaterina E. HeldweinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth B. Draganova Ekaterina E. Heldwein Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
description	Abstract Herpesviruses infect a majority of the human population, establishing lifelong latent infections for which there is no cure. Periodic viral reactivation spreads infection to new hosts while causing various disease states particularly detrimental in the immunocompromised. Efficient viral replication, and ultimately the spread of infection, is dependent on the nuclear egress complex (NEC), a conserved viral heterodimer that helps translocate viral capsids from the nucleus to the cytoplasm where they mature into infectious virions. Here, we have identified peptides, derived from the capsid protein UL25, that are capable of inhibiting the membrane-budding activity of the NEC from herpes simplex virus type 1 in vitro. We show that the inhibitory ability of the peptides depends on their length and the propensity to form an α-helix but not on the exact amino acid sequence. Current therapeutics that target viral DNA replication machinery are rendered ineffective by drug resistance due to viral mutations. Our results establish a basis for the development of an alternative class of inhibitors against nuclear egress, an essential step in herpesvirus replication, potentially expanding the current repertoire of available therapeutics.
format	article
author	Elizabeth B. Draganova Ekaterina E. Heldwein
author_facet	Elizabeth B. Draganova Ekaterina E. Heldwein
author_sort	Elizabeth B. Draganova
title	Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
title_short	Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
title_full	Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
title_fullStr	Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
title_full_unstemmed	Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
title_sort	virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5dc9c39447a54f43b26531225b79a2c5
work_keys_str_mv	AT elizabethbdraganova virusderivedpeptideinhibitorsoftheherpessimplexvirustype1nuclearegresscomplex AT ekaterinaeheldwein virusderivedpeptideinhibitorsoftheherpessimplexvirustype1nuclearegresscomplex
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Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex

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