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 BE., KUMAR A., GANGADHARAN B., ALONZI D., Brun J., HILL M., Bharucha T., Bosworth A., Graham V., Dowall S., MILLER J., ZITZMANN N.
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 re-lated virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. Glycosylation analysis of HAZV has been limited; firstly, we confirmed for the first time the occu-pation of two N-glycosylation sites in the HAZV glycoprotein. Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, determined by quantification of 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 oligosaccharides in un-infected and infected SW13 and uninfected Vero cells. Even so, iminosugars may yet have poten-tial as antivirals for CCHFV since the positions and importance of N-linked glycans may differ be-tween the viruses: a hypothesis requiring further evaluation.