Section of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, Sweden.
Viruses. 2019 Mar 12;11(3):242. doi: 10.3390/v11030242.
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.
流行性角膜结膜炎（EKC）是一种严重的眼部疾病，可导致视力障碍。人腺病毒 37 型（HAdV-D37）是 EKC 的主要病原体之一，它使用含唾液酸（SA）的聚糖作为细胞受体。目前，尚无针对 EKC 的批准抗病毒药物。最近，我们报道了硫酸化糖胺聚糖（GAG）通过病毒纤维蛋白的纤维球（FK）结构域与 HAdV-D37 结合，并作为诱饵受体发挥作用。基于这一发现，我们推测 GAG 模拟物可能作为人工诱饵受体并抑制 HAdV-D37 感染。近年来，重新利用已批准的药物来鉴定新的抗病毒药物引起了极大的关注。在这里，我们报告了苏拉明（一种世界卫生组织批准的药物和一种广为人知的 GAG 模拟物）对 HAdV-D37 的抗病毒作用。市售的苏拉明类似物也显示出对 HAdV-D37 的抗病毒作用。我们证明苏拉明通过抑制 HAdV-D37 与细胞的附着来发挥其抗病毒活性。我们还揭示了苏拉明的抗病毒作用是针对 HAdV 物种特异性的。总的来说，在这项概念验证研究中，我们首次证明病毒与诱饵受体的结合构成了抗病毒药物开发的一个新的和未被探索的目标。
