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Structure, Dynamics, Receptor Binding, and Antibody Binding of Fully-glycosylated Full-length SARS-CoV-2 Spike Protein in a Viral Membrane

Yeol Kyo Choi, Yiwei Cao, View ORCID ProfileMartin Frank, Hyeonuk Woo, Sang-Jun Park, Min Sun Yeom, View ORCID ProfileTristan I. Croll, Chaok Seok, View ORCID ProfileWonpil Im
doi: https://doi.org/10.1101/2020.10.18.343715
Yeol Kyo Choi
1Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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Yiwei Cao
1Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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Martin Frank
2Biognos AB, Box 8963, 40274 Göteborg, Sweden
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Hyeonuk Woo
3Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
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Sang-Jun Park
1Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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Min Sun Yeom
4Korean Institute of Science and Technology Information, Daejeon 34141, Republic of Korea
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Tristan I. Croll
5Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK
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  • ORCID record for Tristan I. Croll
Chaok Seok
3Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
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Wonpil Im
1Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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  • ORCID record for Wonpil Im
  • For correspondence: wonpil@lehigh.edu
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ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates host cell entry by binding to angiotensin-converting enzyme 2 (ACE2), and is considered the major target for drug and vaccine development. We previously built fully-glycosylated full-length SARS-CoV-2 S protein models in a viral membrane including both open and closed conformations of receptor binding domain (RBD) and different templates for the stalk region. In this work, multiple μs-long all-atom molecular dynamics simulations were performed to provide deeper insight into the structure and dynamics of S protein, and glycan functions. Our simulations reveal that the highly flexible stalk is composed of two independent joints and most probable S protein orientations are competent for ACE2 binding. We identify multiple glycans stabilizing the open and/or closed states of RBD, and demonstrate that the exposure of antibody epitopes can be captured by detailed antibody-glycan clash analysis instead of a commonly-used accessible surface area analysis that tends to overestimate the impact of glycan shielding and neglect possible detailed interactions between glycan and antibody. Overall, our observations offer structural and dynamic insight into SARS-CoV-2 S protein and potentialize for guiding the design of effective antiviral therapeutics.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://www.charmm-gui.org/docs/archive/covid19

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 18, 2020.
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Structure, Dynamics, Receptor Binding, and Antibody Binding of Fully-glycosylated Full-length SARS-CoV-2 Spike Protein in a Viral Membrane
Yeol Kyo Choi, Yiwei Cao, Martin Frank, Hyeonuk Woo, Sang-Jun Park, Min Sun Yeom, Tristan I. Croll, Chaok Seok, Wonpil Im
bioRxiv 2020.10.18.343715; doi: https://doi.org/10.1101/2020.10.18.343715
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Structure, Dynamics, Receptor Binding, and Antibody Binding of Fully-glycosylated Full-length SARS-CoV-2 Spike Protein in a Viral Membrane
Yeol Kyo Choi, Yiwei Cao, Martin Frank, Hyeonuk Woo, Sang-Jun Park, Min Sun Yeom, Tristan I. Croll, Chaok Seok, Wonpil Im
bioRxiv 2020.10.18.343715; doi: https://doi.org/10.1101/2020.10.18.343715

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