Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells

(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present...

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Autores principales:	David A. Ostrov, Andrew P. Bluhm, Danmeng Li, Juveriya Qamar Khan, Megha Rohamare, Karthic Rajamanickam, Kalpana K. Bhanumathy, Jocelyne Lew, Darryl Falzarano, Franco J. Vizeacoumar, Joyce A. Wilson, Marco Mottinelli, Siva Rama Raju Kanumuri, Abhisheak Sharma, Christopher R. McCurdy, Michael H. Norris
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	drug discovery sigma-1 receptor SARS-CoV-2 molecular docking antiviral therapeutics Medicine R
Acceso en línea:	https://doaj.org/article/63add6fb9ba140d2866daea0ebf129c3
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spelling	oai:doaj.org-article:63add6fb9ba140d2866daea0ebf129c32021-11-25T18:38:52ZHighly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells10.3390/pathogens101115142076-0817https://doaj.org/article/63add6fb9ba140d2866daea0ebf129c32021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1514https://doaj.org/toc/2076-0817(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.David A. OstrovAndrew P. BluhmDanmeng LiJuveriya Qamar KhanMegha RohamareKarthic RajamanickamKalpana K. BhanumathyJocelyne LewDarryl FalzaranoFranco J. VizeacoumarJoyce A. WilsonMarco MottinelliSiva Rama Raju KanumuriAbhisheak SharmaChristopher R. McCurdyMichael H. NorrisMDPI AGarticledrug discoverysigma-1 receptorSARS-CoV-2molecular dockingantiviral therapeuticsMedicineRENPathogens, Vol 10, Iss 1514, p 1514 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug discovery sigma-1 receptor SARS-CoV-2 molecular docking antiviral therapeutics Medicine R
spellingShingle	drug discovery sigma-1 receptor SARS-CoV-2 molecular docking antiviral therapeutics Medicine R David A. Ostrov Andrew P. Bluhm Danmeng Li Juveriya Qamar Khan Megha Rohamare Karthic Rajamanickam Kalpana K. Bhanumathy Jocelyne Lew Darryl Falzarano Franco J. Vizeacoumar Joyce A. Wilson Marco Mottinelli Siva Rama Raju Kanumuri Abhisheak Sharma Christopher R. McCurdy Michael H. Norris Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
description	(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.
format	article
author	David A. Ostrov Andrew P. Bluhm Danmeng Li Juveriya Qamar Khan Megha Rohamare Karthic Rajamanickam Kalpana K. Bhanumathy Jocelyne Lew Darryl Falzarano Franco J. Vizeacoumar Joyce A. Wilson Marco Mottinelli Siva Rama Raju Kanumuri Abhisheak Sharma Christopher R. McCurdy Michael H. Norris
author_facet	David A. Ostrov Andrew P. Bluhm Danmeng Li Juveriya Qamar Khan Megha Rohamare Karthic Rajamanickam Kalpana K. Bhanumathy Jocelyne Lew Darryl Falzarano Franco J. Vizeacoumar Joyce A. Wilson Marco Mottinelli Siva Rama Raju Kanumuri Abhisheak Sharma Christopher R. McCurdy Michael H. Norris
author_sort	David A. Ostrov
title	Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
title_short	Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
title_full	Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
title_fullStr	Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
title_full_unstemmed	Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
title_sort	highly specific sigma receptor ligands exhibit anti-viral properties in sars-cov-2 infected cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/63add6fb9ba140d2866daea0ebf129c3
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Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells

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