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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
MDPI
2023
|
| _version_ | 1826309580463800320 |
|---|---|
| author | Tyrrell, BE Kumar, A Gangadharan, B Alonzi, D Brun, J Hill, M Bharucha, T Bosworth, A Graham, V Dowall, S Miller, JL Zitzmann, N |
| author_facet | Tyrrell, BE Kumar, A Gangadharan, B Alonzi, D Brun, J Hill, M Bharucha, T Bosworth, A Graham, V Dowall, S Miller, JL Zitzmann, N |
| author_sort | Tyrrell, BE |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T07:36:21Z |
| format | Journal article |
| id | oxford-uuid:5f785034-1fd7-40ae-9b02-f53d8ed725be |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:36:21Z |
| publishDate | 2023 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:5f785034-1fd7-40ae-9b02-f53d8ed725be2023-03-20T10:18:38ZExploring 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 assaysJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5f785034-1fd7-40ae-9b02-f53d8ed725beEnglishSymplectic ElementsMDPI2023Tyrrell, BEKumar, AGangadharan, BAlonzi, DBrun, JHill, MBharucha, TBosworth, AGraham, VDowall, SMiller, JLZitzmann, NCrimean-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. |
| spellingShingle | Tyrrell, BE Kumar, A Gangadharan, B Alonzi, D Brun, J Hill, M Bharucha, T Bosworth, A Graham, V Dowall, S Miller, JL Zitzmann, N 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 |
| work_keys_str_mv | AT tyrrellbe exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT kumara exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT gangadharanb exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT alonzid exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT brunj exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT hillm exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT bharuchat exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT boswortha exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT grahamv exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT dowalls exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT millerjl exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays AT zitzmannn exploringthepotentialofiminosugarsasantiviralsforcrimeancongohaemorrhagicfevervirususingthesurrogatehazaravirusliquidchromatographybasedmappingofviralnglycosylationandinvitroantiviralassays |