Pathology

Receptor

Organic chemistry

Trimer

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Monoclonal antibody

Biology

Pandemic

Binding site

Outbreak

Antibody

Virology

Cryo-electron microscopy

Chemistry

Immunology

Betacoronavirus

Coronavirus

Dimer

2019-20 coronavirus outbreak

Computational biology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Biochemistry

Medicine

Science

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation