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DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses

Although there are effective nucleoside analogs to treat HSV, VZV, and HCMV disease, herpesvirus infections continue to contribute to significant morbidity and mortality. Acyclovir is the drug of choice for HSV encephalopathy, yet there is an estimated 6–19% mortality rate with half of the survivors...

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Autores principales: Keil, Tara, Liu, Dongmei, Lloyd, Megan, Coombs, Wanda, Moffat, Jennifer, Visalli, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434925/
https://www.ncbi.nlm.nih.gov/pubmed/32903425
http://dx.doi.org/10.3389/fmicb.2020.01862
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author Keil, Tara
Liu, Dongmei
Lloyd, Megan
Coombs, Wanda
Moffat, Jennifer
Visalli, Robert
author_facet Keil, Tara
Liu, Dongmei
Lloyd, Megan
Coombs, Wanda
Moffat, Jennifer
Visalli, Robert
author_sort Keil, Tara
collection PubMed
description Although there are effective nucleoside analogs to treat HSV, VZV, and HCMV disease, herpesvirus infections continue to contribute to significant morbidity and mortality. Acyclovir is the drug of choice for HSV encephalopathy, yet there is an estimated 6–19% mortality rate with half of the survivors experiencing moderate to severe chronic neurological deficits. For VZV, current treatments are inadequate to prevent acute and persistent pain due to zoster. Treatment of HCMV with GCV requires close monitoring particularly in patients with impaired renal function and there are no approved treatments for congenital HCMV infections. New therapeutic options to control cytomegalovirus reactivation in bone marrow and stem cell transplant patients are needed to improve patient outcome. No successful chemotherapeutic options are available for EBV, HHV-6, 7, and 8. Drug resistance is a concern for HCMV, HSV, and VZV since approved drugs share common mechanisms of action. Targeting DNA encapsidation or capsid assembly provide additional options for the development of non-nucleoside, small molecule anti-herpesviral drugs.
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spelling pubmed-74349252020-09-03 DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses Keil, Tara Liu, Dongmei Lloyd, Megan Coombs, Wanda Moffat, Jennifer Visalli, Robert Front Microbiol Microbiology Although there are effective nucleoside analogs to treat HSV, VZV, and HCMV disease, herpesvirus infections continue to contribute to significant morbidity and mortality. Acyclovir is the drug of choice for HSV encephalopathy, yet there is an estimated 6–19% mortality rate with half of the survivors experiencing moderate to severe chronic neurological deficits. For VZV, current treatments are inadequate to prevent acute and persistent pain due to zoster. Treatment of HCMV with GCV requires close monitoring particularly in patients with impaired renal function and there are no approved treatments for congenital HCMV infections. New therapeutic options to control cytomegalovirus reactivation in bone marrow and stem cell transplant patients are needed to improve patient outcome. No successful chemotherapeutic options are available for EBV, HHV-6, 7, and 8. Drug resistance is a concern for HCMV, HSV, and VZV since approved drugs share common mechanisms of action. Targeting DNA encapsidation or capsid assembly provide additional options for the development of non-nucleoside, small molecule anti-herpesviral drugs. Frontiers Media S.A. 2020-08-12 /pmc/articles/PMC7434925/ /pubmed/32903425 http://dx.doi.org/10.3389/fmicb.2020.01862 Text en Copyright © 2020 Keil, Liu, Lloyd, Coombs, Moffat and Visalli. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Keil, Tara
Liu, Dongmei
Lloyd, Megan
Coombs, Wanda
Moffat, Jennifer
Visalli, Robert
DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title_full DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title_fullStr DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title_full_unstemmed DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title_short DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses
title_sort dna encapsidation and capsid assembly are underexploited antiviral targets for the treatment of herpesviruses
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434925/
https://www.ncbi.nlm.nih.gov/pubmed/32903425
http://dx.doi.org/10.3389/fmicb.2020.01862
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