tetano
Editor, Senior Moderator
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
See all authors and affiliations
Science 19 Feb 2020:
eabb2507
DOI: 10.1126/science.abb2507
[h=2]Abstract[/h] The outbreak of a novel betacoronavirus (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 (MCM) development, we determined a 3.5 ?-resolution cryo-EM 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 show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than 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 antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.
https://science.sciencemag.org/cont..._Sbu6NnYbvzlt9MhkUjNMLX-ftAqeyYBxgvlPsEYRP2V0
- Daniel Wrapp[SUP]1[/SUP],*,
- Nianshuang Wang[SUP]1[/SUP],*,
- Kizzmekia S. Corbett[SUP]2[/SUP],
- Jory A. Goldsmith[SUP]1[/SUP],
- Ching-Lin Hsieh[SUP]1[/SUP],
- Olubukola Abiona[SUP]2[/SUP],
- Barney S. Graham[SUP]2[/SUP],
- Jason S. McLellan[SUP]1[/SUP],†
See all authors and affiliations
Science 19 Feb 2020:
eabb2507
DOI: 10.1126/science.abb2507
[h=2]Abstract[/h] The outbreak of a novel betacoronavirus (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 (MCM) development, we determined a 3.5 ?-resolution cryo-EM 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 show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than 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 antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.
https://science.sciencemag.org/cont..._Sbu6NnYbvzlt9MhkUjNMLX-ftAqeyYBxgvlPsEYRP2V0