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Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants.
Science. 2021 08 06; 373(6555):642-648.Sci

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.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

34168070

Citation

Cai, Yongfei, et al. "Structural Basis for Enhanced Infectivity and Immune Evasion of SARS-CoV-2 Variants." Science (New York, N.Y.), vol. 373, no. 6555, 2021, pp. 642-648.
Cai Y, Zhang J, Xiao T, et al. Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science. 2021;373(6555):642-648.
Cai, Y., Zhang, J., Xiao, T., Lavine, C. L., Rawson, S., Peng, H., Zhu, H., Anand, K., Tong, P., Gautam, A., Lu, S., Sterling, S. M., Walsh, R. M., Rits-Volloch, S., Lu, J., Wesemann, D. R., Yang, W., Seaman, M. S., & Chen, B. (2021). Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science (New York, N.Y.), 373(6555), 642-648. https://doi.org/10.1126/science.abi9745
Cai Y, et al. Structural Basis for Enhanced Infectivity and Immune Evasion of SARS-CoV-2 Variants. Science. 2021 08 6;373(6555):642-648. PubMed PMID: 34168070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. AU - Cai,Yongfei, AU - Zhang,Jun, AU - Xiao,Tianshu, AU - Lavine,Christy L, AU - Rawson,Shaun, AU - Peng,Hanqin, AU - Zhu,Haisun, AU - Anand,Krishna, AU - Tong,Pei, AU - Gautam,Avneesh, AU - Lu,Shen, AU - Sterling,Sarah M, AU - Walsh,Richard M,Jr AU - Rits-Volloch,Sophia, AU - Lu,Jianming, AU - Wesemann,Duane R, AU - Yang,Wei, AU - Seaman,Michael S, AU - Chen,Bing, Y1 - 2021/06/24/ PY - 2021/04/12/received PY - 2021/06/15/accepted PY - 2021/6/26/pubmed PY - 2021/8/14/medline PY - 2021/6/25/entrez SP - 642 EP - 648 JF - Science (New York, N.Y.) JO - Science VL - 373 IS - 6555 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34168070/Structural_basis_for_enhanced_infectivity_and_immune_evasion_of_SARS-CoV-2_variants. DB - PRIME DP - Unbound Medicine ER -