Modeling Attachment Factor Used in Flaviviral Entry

Abstract

Flavivirus is a genus of positive-sense single-stranded RNA viruses that are mostly transmitted through mosquito or tick vectors and are known to be emerging and re-emerging viruses. Some of the significant species that have been reported to cause an outbreak globally include DENV, YFV, WNV, ZIKV and JEV. While some vaccines have been successful in preventing infections caused by certain flaviviruses, specific treatments and vaccines for the majority of flaviviruses are yet to be found. The early process of viral infection requires the binding of the viral surface protein, specifically the envelope protein, to a host cell receptor. Although their mechanism of neuroinvasion is still unknown, flaviviruses, including the aforementioned species, utilize the ubiquitous Glycosaminoglycans (GAGs), particularly heparan sulfate, as attachment factors to bind to the host cell. GAGs are long chains of polysaccharides composed of repeating units of sugar molecules, and there are different types including heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, and hyaluronic acid. Given the importance of GAGs in viral attachment, a comprehensive understanding of the biology and pathogenesis of flavivirus is crucial in identifying potential treatments. Hence, this study aims to investigate the role of heparin in flavivirus infection on SH-sy5y cells through luciferase assay. The results showed that pre-treating the virus significantly inhibited the infection on SH-sy5y cells. These findings can be beneficial for future references in the discovery of treatments against flavivirus.