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
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
Beatrice E. Tyrrell
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Abhinav Kumar
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Bevin Gangadharan
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Dominic Alonzi
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Juliane Brun
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Michelle Hill
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Tehmina Bharucha
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Andrew Bosworth
UK Health Security Agency (UKHSA), Porton Down, Salisbury SP4 0JG, UK
Victoria Graham
UK Health Security Agency (UKHSA), Porton Down, Salisbury SP4 0JG, UK
Stuart Dowall
UK Health Security Agency (UKHSA), Porton Down, Salisbury SP4 0JG, UK
Joanna L. Miller
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
Nicole Zitzmann
Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
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.
