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Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays

Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. Hazara virus (HAZV) is a genetically and serologically related virus that has been...

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Autores principales: Tyrrell, Beatrice E., Kumar, Abhinav, Gangadharan, Bevin, Alonzi, Dominic, Brun, Juliane, Hill, Michelle, Bharucha, Tehmina, Bosworth, Andrew, Graham, Victoria, Dowall, Stuart, Miller, Joanna L., Zitzmann, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057787/
https://www.ncbi.nlm.nih.gov/pubmed/36986321
http://dx.doi.org/10.3390/pathogens12030399
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author Tyrrell, Beatrice E.
Kumar, Abhinav
Gangadharan, Bevin
Alonzi, Dominic
Brun, Juliane
Hill, Michelle
Bharucha, Tehmina
Bosworth, Andrew
Graham, Victoria
Dowall, Stuart
Miller, Joanna L.
Zitzmann, Nicole
author_facet Tyrrell, Beatrice E.
Kumar, Abhinav
Gangadharan, Bevin
Alonzi, Dominic
Brun, Juliane
Hill, Michelle
Bharucha, Tehmina
Bosworth, Andrew
Graham, Victoria
Dowall, Stuart
Miller, Joanna L.
Zitzmann, Nicole
author_sort Tyrrell, Beatrice E.
collection PubMed
description Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation.
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spelling pubmed-100577872023-03-30 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays Tyrrell, Beatrice E. Kumar, Abhinav Gangadharan, Bevin Alonzi, Dominic Brun, Juliane Hill, Michelle Bharucha, Tehmina Bosworth, Andrew Graham, Victoria Dowall, Stuart Miller, Joanna L. Zitzmann, Nicole Pathogens Article Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. MDPI 2023-03-01 /pmc/articles/PMC10057787/ /pubmed/36986321 http://dx.doi.org/10.3390/pathogens12030399 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tyrrell, Beatrice E.
Kumar, Abhinav
Gangadharan, Bevin
Alonzi, Dominic
Brun, Juliane
Hill, Michelle
Bharucha, Tehmina
Bosworth, Andrew
Graham, Victoria
Dowall, Stuart
Miller, Joanna L.
Zitzmann, Nicole
Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title_full Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title_fullStr Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title_full_unstemmed Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title_short Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays
title_sort exploring the potential of iminosugars as antivirals for crimean-congo haemorrhagic fever virus, using the surrogate hazara virus: liquid-chromatography-based mapping of viral n-glycosylation and in vitro antiviral assays
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057787/
https://www.ncbi.nlm.nih.gov/pubmed/36986321
http://dx.doi.org/10.3390/pathogens12030399
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