02799nas a2200661   4500000000100000000000100001008004100002260001500043653003600058653001200094653002000106653001800126653001300144653002500157653002700182653001100209653001100220653000900231653001400240653001400254653002700268653002100295653002100316653002500337653001500362653003600377653001500413653003600428653001800464653002000482653001100502653005000513653002400563653001400587100002000601700001600621700001900637700002300656700002100679700001700700700002300717700001800740700002800758700001900786700002200805700002300827700001600850700002200866700001600888700002100904700001700925700002300942245010800965300001501073490000801088520102701096022001402123       2020                            d  c2020-05-1410aAngiotensin-Converting Enzyme 210aAnimals10aBetacoronavirus10aBlood Vessels10aCOVID-1910aChlorocebus aethiops10aCoronavirus Infections10aHumans10akidney10aMice10aorganoids10aPandemics10aPeptidyl-Dipeptidase A10aPneumonia, Viral10aReceptors, Virus10aRecombinant Proteins10aSARS-CoV-210aSpike Glycoprotein, Coronavirus10aVero Cells10aangiotensin converting enzyme 210aBlood Vessels10ahuman organoids10akidney10asevere acute respiratory syndrome coronavirus10aspike glycoproteins10atreatment1 aVanessa Monteil1 aHyesoo Kwon1 aPatricia Prado1 aAstrid Hagelkrüys1 aReiner A. Wimmer1 aMartin Stahl1 aAlexandra Leopoldi1 aElena Garreta1 aCarmen Hurtado Del Pozo1 aFelipe Prosper1 aJuan Pablo Romero1 aGerald Wirnsberger1 aHaibo Zhang1 aArthur S. Slutsky1 aRyan Conder1 aNuria Montserrat1 aAli Mirazimi1 aJosef M. Penninger00aInhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2  a905-913.e70 v1813 aWe 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.  a1097-4172