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Pressurized DNA state inside herpes capsids—A novel antiviral target
Drug resistance in viruses represents one of the major challenges of healthcare. As part of an effort to provide a treatment that avoids the possibility of drug resistance, we discovered a novel mechanism of action (MOA) and specific compounds to treat all nine human herpesviruses and animal herpesv...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377361/ https://www.ncbi.nlm.nih.gov/pubmed/32702029 http://dx.doi.org/10.1371/journal.ppat.1008604 |
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author | Brandariz-Nuñez, Alberto Robinson, Scott J. Evilevitch, Alex |
author_facet | Brandariz-Nuñez, Alberto Robinson, Scott J. Evilevitch, Alex |
author_sort | Brandariz-Nuñez, Alberto |
collection | PubMed |
description | Drug resistance in viruses represents one of the major challenges of healthcare. As part of an effort to provide a treatment that avoids the possibility of drug resistance, we discovered a novel mechanism of action (MOA) and specific compounds to treat all nine human herpesviruses and animal herpesviruses. The novel MOA targets the pressurized genome state in a viral capsid, “turns off” capsid pressure, and blocks viral genome ejection into a cell nucleus, preventing viral replication. This work serves as a proof-of-concept to demonstrate the feasibility of a new antiviral target—suppressing pressure-driven viral genome ejection—that is likely impervious to developing drug resistance. This pivotal finding presents a platform for discovery of a new class of broad-spectrum treatments for herpesviruses and other viral infections with genome-pressure-dependent replication. A biophysical approach to antiviral treatment such as this is also a vital strategy to prevent the spread of emerging viruses where vaccine development is challenged by high mutation rates or other evasion mechanisms. |
format | Online Article Text |
id | pubmed-7377361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73773612020-08-12 Pressurized DNA state inside herpes capsids—A novel antiviral target Brandariz-Nuñez, Alberto Robinson, Scott J. Evilevitch, Alex PLoS Pathog Research Article Drug resistance in viruses represents one of the major challenges of healthcare. As part of an effort to provide a treatment that avoids the possibility of drug resistance, we discovered a novel mechanism of action (MOA) and specific compounds to treat all nine human herpesviruses and animal herpesviruses. The novel MOA targets the pressurized genome state in a viral capsid, “turns off” capsid pressure, and blocks viral genome ejection into a cell nucleus, preventing viral replication. This work serves as a proof-of-concept to demonstrate the feasibility of a new antiviral target—suppressing pressure-driven viral genome ejection—that is likely impervious to developing drug resistance. This pivotal finding presents a platform for discovery of a new class of broad-spectrum treatments for herpesviruses and other viral infections with genome-pressure-dependent replication. A biophysical approach to antiviral treatment such as this is also a vital strategy to prevent the spread of emerging viruses where vaccine development is challenged by high mutation rates or other evasion mechanisms. Public Library of Science 2020-07-23 /pmc/articles/PMC7377361/ /pubmed/32702029 http://dx.doi.org/10.1371/journal.ppat.1008604 Text en © 2020 Brandariz-Nuñez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Brandariz-Nuñez, Alberto Robinson, Scott J. Evilevitch, Alex Pressurized DNA state inside herpes capsids—A novel antiviral target |
title | Pressurized DNA state inside herpes capsids—A novel antiviral target |
title_full | Pressurized DNA state inside herpes capsids—A novel antiviral target |
title_fullStr | Pressurized DNA state inside herpes capsids—A novel antiviral target |
title_full_unstemmed | Pressurized DNA state inside herpes capsids—A novel antiviral target |
title_short | Pressurized DNA state inside herpes capsids—A novel antiviral target |
title_sort | pressurized dna state inside herpes capsids—a novel antiviral target |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377361/ https://www.ncbi.nlm.nih.gov/pubmed/32702029 http://dx.doi.org/10.1371/journal.ppat.1008604 |
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