Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

Yongfei Cai; Jun Zhang; Tianshu Xiao; Christy L Lavine; Shaun Rawson; Hanqin Peng; Haisun Zhu; Krishna Anand; Pei Tong; Avneesh Gautam; Shen Lu; Sarah M Sterling; Richard M Walsh Jr; Sophia Rits-Volloch; Jianming Lu; Duane R Wesemann; Wei Yang; Michael S Seaman; Bing Chen

doi:10.1126/science.abi9745

Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

Science. 2021 Aug 6;373(6555):642-648. doi: 10.1126/science.abi9745. Epub 2021 Jun 24.

Authors

Yongfei Cai^#^{1

2}, Jun Zhang^#^{1

2}, Tianshu Xiao^#^{1

2}, Christy L Lavine³, Shaun Rawson^{4

5

6}, Hanqin Peng¹, Haisun Zhu⁷, Krishna Anand⁷, Pei Tong⁸, Avneesh Gautam⁸, Shen Lu⁹, Sarah M Sterling^{5

6}, Richard M Walsh Jr^{5

6}, Sophia Rits-Volloch¹, Jianming Lu^{9

10}, Duane R Wesemann⁸, Wei Yang⁷, Michael S Seaman³, Bing Chen^{11

2}

Affiliations

¹ Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115, USA.
² Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.
³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
⁴ SBGrid Consortium, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
⁵ The Harvard Cryo-EM Center for Structural Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
⁶ Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
⁷ Institute for Protein Innovation, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA.
⁸ Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
⁹ Codex BioSolutions, Inc., 401 Professional Drive, Gaithersburg, MD 20879, USA.
¹⁰ Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, 3900 Reservoir Road, NW, Washington, DC 20057, USA.
¹¹ Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115, USA. bchen@crystal.harvard.edu.

^# Contributed equally.

Abstract

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Angiotensin-Converting Enzyme 2 / metabolism
Antibodies, Viral / immunology
Antigens, Viral / immunology
COVID-19 / virology*
Cryoelectron Microscopy
HEK293 Cells
Humans
Immune Evasion*
Models, Molecular
Mutation
Protein Binding
Protein Conformation
Protein Domains
Protein Interaction Domains and Motifs
Protein Subunits / chemistry
Receptors, Coronavirus / metabolism
SARS-CoV-2 / chemistry*
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology
SARS-CoV-2 / pathogenicity*
Spike Glycoprotein, Coronavirus / chemistry*
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*
Spike Glycoprotein, Coronavirus / metabolism

Substances

Antibodies, Viral
Antigens, Viral
Protein Subunits
Receptors, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
ACE2 protein, human
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding