Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus

Viruses

Naresh Chandra¹  Lars Frängsmyr¹  Niklas Arnberg¹ 

[1] Section of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, Sweden;

关键词: glycosaminoglycans;    adenovirus;    cellular receptor;    decoy receptor;    epidemic keratoconjunctivitis;    GAG-mimetic;   

DOI  :  10.3390/v11030242

来源: DOAJ

【 摘 要 】

Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.

【 授权许可】

Unknown