The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus . This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses.

中文翻译：

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α-dystroglycan N 末端是一种针对 SARS-CoV-2 和包膜病毒的广谱抗病毒剂

COVID-19 大流行表明需要开发有效的治疗方法，以应对对人类健康构成重大威胁的病毒感染的进一步流行。作为天然复合抗病毒候选药物，我们重点关注α-肌营养不良聚糖，这是一种高度糖基化的基底膜蛋白，可将细胞外基质与细胞内细胞骨架连接起来。在这里，我们表明，在没有翻译后修饰的情况下产生的 α-dystroglycan (α-DGN) 的 N 末端片段可以阻止细胞培养物、人类原代肠道类器官和肺部中 SARS-CoV-2 的感染表达人类受体血管紧张素 I 转换酶 2 (hACE2) 的转基因小鼠。 α-DGN 的预防性和治疗性给药可降低 SARS-CoV-2 肺滴度，并保护小鼠免受呼吸道症状和死亡。重组α-DGN还可以阻断多种包膜病毒的感染，包括四种登革热病毒血清型、甲型流感病毒、呼吸道合胞病毒、蜱传脑炎病毒，但不能阻断人类腺病毒（一种无包膜病毒）。这项研究将可溶性重组 α-DGN 作为一种针对包膜病毒的宽带天然化合物候选治疗剂。