Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

TLDR

Spike proteins of coronaviruses, including SARS‑CoV, use cellular receptors to mediate infection of target cells. The study aims to identify the receptor that SARS‑CoV uses to enter cells. The authors isolated the metallopeptidase ACE2 from SARS‑CoV‑permissive Vero E6 cells and demonstrated that it binds the S1 domain of the viral spike protein. Soluble ACE2, but not ACE1, blocks S1 binding; ACE2‑transfected 293T cells form syncytia with spike‑expressing cells and support efficient viral replication, while anti‑ACE2 antibodies inhibit replication on Vero E6 cells, confirming ACE2 as a functional SARS‑CoV receptor.

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. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), 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.