Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

Summary: Currently available SARS-CoV-2 therapeutics are targeted toward moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. Although vaccines have demonstrated protective efficacy, vaccine hesitancy a...

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Autores principales:	Ria Goswami, Veronica S. Russell, Joshua J. Tu, Charlene Thomas, Philip Hughes, Francine Kelly, Stephanie N. Langel, Justin Steppe, Scott M. Palmer, Timothy Haystead, Maria Blasi, Sallie R. Permar
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Therapeutics Virology Science Q
Acceso en línea:	https://doaj.org/article/ee780399eaa745259751f63b2147a779
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spelling	oai:doaj.org-article:ee780399eaa745259751f63b2147a7792021-11-26T04:37:34ZOral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells2589-004210.1016/j.isci.2021.103412https://doaj.org/article/ee780399eaa745259751f63b2147a7792021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013833https://doaj.org/toc/2589-0042Summary: Currently available SARS-CoV-2 therapeutics are targeted toward moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. Although vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways previously associated with poor SARS-CoV-2 disease outcomes. In addition, SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.Ria GoswamiVeronica S. RussellJoshua J. TuCharlene ThomasPhilip HughesFrancine KellyStephanie N. LangelJustin SteppeScott M. PalmerTimothy HaysteadMaria BlasiSallie R. PermarElsevierarticleTherapeuticsVirologyScienceQENiScience, Vol 24, Iss 12, Pp 103412- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics Virology Science Q
spellingShingle	Therapeutics Virology Science Q Ria Goswami Veronica S. Russell Joshua J. Tu Charlene Thomas Philip Hughes Francine Kelly Stephanie N. Langel Justin Steppe Scott M. Palmer Timothy Haystead Maria Blasi Sallie R. Permar Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
description	Summary: Currently available SARS-CoV-2 therapeutics are targeted toward moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. Although vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways previously associated with poor SARS-CoV-2 disease outcomes. In addition, SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.
format	article
author	Ria Goswami Veronica S. Russell Joshua J. Tu Charlene Thomas Philip Hughes Francine Kelly Stephanie N. Langel Justin Steppe Scott M. Palmer Timothy Haystead Maria Blasi Sallie R. Permar
author_facet	Ria Goswami Veronica S. Russell Joshua J. Tu Charlene Thomas Philip Hughes Francine Kelly Stephanie N. Langel Justin Steppe Scott M. Palmer Timothy Haystead Maria Blasi Sallie R. Permar
author_sort	Ria Goswami
title	Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
title_short	Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
title_full	Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
title_fullStr	Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
title_full_unstemmed	Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
title_sort	oral hsp90 inhibitor snx-5422 attenuates sars-cov-2 replication and dampens inflammation in airway cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ee780399eaa745259751f63b2147a779
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Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

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