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

Overview

Journal Pathogens

Date 2023 Mar 29

PMID 36986321

Authors

Beatrice E Tyrrell

Abhinav Kumar

Bevin Gangadharan

Dominic Alonzi

Juliane Brun

Michelle Hill

Tehmina Bharucha

Andrew Bosworth

Victoria Graham

Stuart Dowall

Joanna L Miller

Nicole Zitzmann

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Purification and characterization of soluble recombinant Crimean-Congo hemorrhagic fever virus glycoprotein Gc expressed in mammalian 293F cells.

Makoah N, Litabe M, Simo F, Maboho K, Burt F BMC Biotechnol. 2024; 24(1):59.

PMID: 39192233 PMC: 11348531. DOI: 10.1186/s12896-024-00885-y.

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