1. Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics),
2. Perlmutter Laboratory, Pulmonary Division, Children's Hospital, Department of Pediatrics,
3. Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
4. Tufts University Core Facility, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
5. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

Correspondence to: Hyeryun Choe²Michael Farzan¹ Email: hyeryun.choe@tch.harvard.edu
Email: farzan@mbcrr.harvard.edu

Abstract

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells^{1, 2}. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2)^{3, 4}, isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.