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Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.
Zhao, Peng; Praissman, Jeremy L; Grant, Oliver C; Cai, Yongfei; Xiao, Tianshu; Rosenbalm, Katelyn E; Aoki, Kazuhiro; Kellman, Benjamin P; Bridger, Robert; Barouch, Dan H; Brindley, Melinda A; Lewis, Nathan E; Tiemeyer, Michael; Chen, Bing; Woods, Robert J; Wells, Lance.
  • Zhao P; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Praissman JL; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Grant OC; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Cai Y; Division of Molecular Medicine, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Xiao T; Division of Molecular Medicine, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Rosenbalm KE; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Aoki K; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Kellman BP; Departments of Pediatrics and Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Bridger R; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Brindley MA; Department of Infectious Diseases, Department of Population Health, Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
  • Lewis NE; Departments of Pediatrics and Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at UC San Diego, La Jolla, CA 92093, USA.
  • Tiemeyer M; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Chen B; Division of Molecular Medicine, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Woods RJ; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA. Electronic address: rwoods@ccrc.uga.edu.
  • Wells L; Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of Georgia, Athens, GA 30602, USA. Electronic address: lwells@ccrc.uga.edu.
Cell Host Microbe ; 28(4): 586-601.e6, 2020 10 07.
Article in English | MEDLINE | ID: covidwho-741138
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ABSTRACT
The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatics analyses of natural variants and with existing 3D structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein both alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation. Taken together, these data can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A / Spike Glycoprotein, Coronavirus / Betacoronavirus Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article Affiliation country: J.chom.2020.08.004

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A / Spike Glycoprotein, Coronavirus / Betacoronavirus Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article Affiliation country: J.chom.2020.08.004