Journal Article

Structural basis of receptor recognition by SARS-CoV-2

Auerbach, Ashley, Ye, Gang, Li, Fang, Aihara, Hideki, Wan, Yushun, Shi, Ke, Luo, Chuming, Shang, Jian, Geng, Qibin

2020

Overview

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19 1 , 2 . A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans 3 , 4 . Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2. The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/596/2078 / 631/326/596/4130 / 631/535/1266 / 82 / 82/103 / ACE2 / Analysis / Angiotensin / Angiotensin converting enzyme / Angiotensin-Converting Enzyme 2 / Animals / Betacoronavirus - chemistry / Betacoronavirus - drug effects / Betacoronavirus - metabolism / Binding / Binding Sites / China - epidemiology / Chiroptera - virology / Coronaviridae / Coronavirus - chemistry / Coronavirus - isolation & purification / Coronavirus Infections - drug therapy / Coronavirus Infections - epidemiology / Coronavirus Infections - transmission / Coronavirus Infections - virology / Coronaviruses / COVID-19 / Crystal structure / Crystallization / Crystallography, X-Ray / Crystals / Disease hot spots / Disease Reservoirs - virology / Disease transmission / Eutheria - virology / Host range / Humanities and Social Sciences / Humans / Hydrogen bonds / Infectivity / Membrane proteins / Models, Molecular / multidisciplinary / Pandemics / Pathogenesis / Peptidyl-dipeptidase A / Peptidyl-Dipeptidase A - chemistry / Peptidyl-Dipeptidase A - metabolism / Pneumonia, Viral - drug therapy / Pneumonia, Viral - epidemiology / Pneumonia, Viral - transmission / Pneumonia, Viral - virology / Protein Binding / Protein Domains / Protein Stability / Proteins / Radioligand assay / Receptors / Receptors, Virus - chemistry / Receptors, Virus - metabolism / SARS-CoV-2 / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Severe acute respiratory syndrome-related coronavirus - chemistry / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - metabolism / Spike protein / Structure / Target recognition / Viral diseases / Viruses / Zoonoses - epidemiology / Zoonoses - transmission / Zoonoses - virology