Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

Monteil, Vanessa; Kwon, Hyesoo; Prado, Patricia; Hagelkrüys, Astrid; Wimmer, Reiner; Ståhl, Martin; Leopoldi, Alexandra; Garreta, Elena; Pozo, Carmen Hurtado del; Prósper, Felipe; Romero, Juan Pablo; Wirnsberger, Gerald; Zhang, Haibo; Slutsky, Arthur S.; Conder, Ryan; Montserrat, Núria; Mirazimi, Alì; Penninger, Josef

doi:10.1016/j.cell.2020.04.004

Cited by 1,916 publications

(2,134 citation statements)

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“…Our analysis of single cell RNA-Seq data suggested that ACE2 is positively, though weakly, expressed in the endothelial cells. In another study, ACE2 expression was previously detected in blood vessels (25), and a recent study showed that SARS-CoV-2 is capable of directly infecting blood vessel cells (11). Based on the present finding angiogenesis/blood vessel morphogenesis may be considered a putative function for ACE2 in addition to its classical role as the key angiotensin-(1-7) forming enzyme (59).…”

Section: Discussionsupporting

confidence: 64%

“…A recent preprint report suggested that soluble ACE2 fused to the Fc portion of immunoglobulin can neutralize SARS-CoV-2 in vitro (10). This result was further confirmed by showing that human recombinant soluble ACE2 reduced SARS-CoV-2 infection on cultured Vero-E6 cells in a dose dependent manner (11). Therefore, ACE2 also holds promise for treating patients with coronavirus infection.…”

Section: Introductionmentioning

confidence: 80%

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Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Barker

Parkkila

2020

Preprint

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The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide.COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression, putative functions, and transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung specimens. Single cell RNA-Seq data indicated positive signals along the respiratory tract in the key protective cell types including the goblet and ciliary epithelial cells, as well as in the endothelial cells and type I pneumocytes. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. A novel tool for the prediction of transcription factor binding sites identified several putative sites for determined transcription factors within the ACE2 gene promoter. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 80%

Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Barker

Parkkila

2020

Preprint

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“…Soluble ACE2 has been studied in a phase II trial of ARDS, but largescale, well-powered clinical outcomes trials are needed (33). Research is ongoing to determine whether soluble ACE2 may act as a specific therapeutic to SARS-CoV2 in the role of a decoy receptor, as discussed later (34).…”

Section: Pathogenesis: Angiotensin-converting Enzymementioning

confidence: 99%

COVID-19 for the Cardiologist

Atri

Siddiqi

Lang

et al. 2020

JACC: Basic to Translational Science

252

121

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Highlights-Severe acute respiratory virus-2 (SARS-CoV2), the infection responsible for coronavirus disease-2019 (COVID-19), has spread globally leading to a devastating loss of life. In a few short months, the clinical and scientific communities have rallied to rapidly evolve our understanding of the mechanism(s) of disease and potential therapeutics. -This review discusses the current understanding of the basis virology of SARS-CoV2 and the epidemiology, clinical manifestations, including cardiovascular, and mortality of COVID-19. A detailed review of the viral life cycle and putative mechanism(s) of injury frames the discussion of possible preventative and therapeutic strategies. -The ongoing, unprecedented collective effort will, without a doubt, advance our ability to prevent the spread and optimally care for patients suffering from COVID-19. SummaryThe coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease.We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.

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“…Some groups suggested using circulating soluble ACE2 to capture as many viruses as possible in plasma, restricting their fixation on cell-membrane ACE2 and thus limiting cell infection. In-vitro studies showed that genetically engineered recombinant soluble ACE2 could be a useful therapeutic option (20,31). Moreover, soluble ACE2 might favor the angiotensin-(1-7)/ACE2/MasR pathway over the angiotensin II/ACE/AT1R/aldosterone pathway, preventing or treating severe inflammatory tissue lesions.…”

Section: -Ace2 and Covid-19mentioning

confidence: 99%