Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19.

由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的 2019 冠状病毒病 (COVID-19) 已发展成为全球大流行，迄今为止只有少数抗病毒治疗方法获得批准。血管紧张素转换酶 2 (ACE2) 在 SARS-CoV-2 发病机制中发挥着重要作用，因为它允许病毒进入宿主细胞。在这里，我们表明，源自人肺球状细胞（LSC）的 ACE2 纳米诱饵可以结合并中和 SARS-CoV-2，并保护宿主肺细胞免受感染。在小鼠中，这些 LSC 纳米节点通过吸入疗法递送，并在递送后在肺部停留超过 72 小时。此外，吸入 LSC 纳米颗粒可加速 SARS-CoV-2 模拟物从肺部的清除，且未观察到毒性。在受到活 SARS-CoV-2 攻击的食蟹猴中，吸入四剂此类纳米诱饵可促进病毒清除并减少肺损伤。我们的结果表明 LSC-nanodecoys 可以作为治疗 COVID-19 的潜在治疗剂。