Abstract
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.
Highlights
Outbreaks of emerging infectious diseases continue to challenge human health
Because angiotensin converting enzyme 2 (ACE2) is the SARSCoV-2 receptor, we wanted to provide direct evidence that clinical-grade human recombinant soluble ACE2 (hrsACE2) can interfere with SARS-CoV-2 infections
We infected Vero-E6 cells with different numbers of SARS-CoV-2: 103 plaque-forming units (PFUs; MOI 0.02), PFUs (MOI 2), and
Summary
Outbreaks of emerging infectious diseases continue to challenge human health. The reported incidence of emerging and re-emerging zoonotic disease is increasing in many parts of the world. In December 2019, a novel coronavirus (SARS-CoV-2) crossed species barriers to infect humans (Gorbalenya et al, 2020) and was effectively transmitted from person to person, leading to a pneumonia outbreak first reported in Wuhan, China (Guan et al, 2020; Jiang et al, 2020; Zhou et al, 2020b). This virus causes coronavirus disease-19 (COVID-19) with influenza-like symptoms ranging from mild disease to severe lung injury and multi-organ failure, eventually leading to death, especially in older patients with other co-morbidities. The SARS-CoV-2 pandemic is an enormous burden to public health but has already markedly affected civil societies and the global economy
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