Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
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DOI：
10.1016/j.cell.2020.04.004
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发表时间：
2020-05-14
期刊：
影响因子：
64.5
通讯作者：
Penninger, Josef M.
中科院分区：
文献类型：
--
作者：
Monteil, Vanessa;Kwon, Hyesoo;Penninger, Josef M.
我们先前已经提供了第一个遗传学证据，证明血管紧张素转换酶2(ACE2)是严重急性呼吸综合征冠状病毒(SARS-CoV)的关键受体，ACE2保护肺免受损伤，为SARS-CoV感染导致严重肺衰竭和死亡提供了分子解释。ACE2现在也被认为是SARS-CoV-2感染的关键受体，有人建议抑制这种相互作用可能用于治疗新冠肺炎患者。然而，目前尚不清楚人重组可溶性ACE2(HrsACE2)是否能抑制SARS-CoV-2的生长。在这里，我们表明临床分级的hrsACE2使Vero细胞中SARS-CoV-2的恢复减少了1000-5000倍。同等的小鼠rsACE2没有任何影响。我们还发现SARS-CoV-2可以直接感染工程化的人血管类器官和人肾类器官，hrsACE2可以抑制这种作用。这些数据表明，hrsACE2可以显著阻断SARS-CoV-2感染的早期阶段。
We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.