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. 2020 Aug 5;15(8):e0237295.
doi: 10.1371/journal.pone.0237295. eCollection 2020.

Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain

Austen Bernardi  1 , Yihan Huang  2 , Bradley Harris  1 , Yongao Xiong  1 , Somen Nandi  1   3 , Karen A McDonald  1   3 , Roland Faller  1
Affiliations

Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain

Austen Bernardi et al. PLoS One. .

Abstract

We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Proposed strategy for SARS-CoV-2 neutralization by ACE2-Fc immunoadhesin.
ACE2-Fc binds to the spike (S) protein on the virus and blocks binding to the human cellular receptor ACE2, preventing cellular entrance of SARS-CoV-2.
Fig 2
Fig 2. Infographic of the ACE2-Fc variant 1 homodimer bound to two SpFr.
Fig 3
Fig 3. Glycans used in the simulated systems.
All structures were built using GlycanBuilder [37].
Fig 4
Fig 4
Initial (left) and 75 ns simulated (right) configurations of all systems.
Fig 5
Fig 5
Backbone RMSD profiles of ACE2 (top) and Fc (bottom) ordered domains referenced to initial and final simulation configurations. ACE2: residues 4–707. Fc: residues 745–950. (see S1 File).
See this image and copyright information in PMC

References

    1. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–9. 10.1038/s41586-020-2008-3 - DOI - PMC - PubMed
    1. Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochemical and Biophysical Research Communications. 2020;525(1):135–40. - PMC - PubMed
    1. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nature Medicine. 2020;26(4):450–2. 10.1038/s41591-020-0820-9 - DOI - PMC - PubMed
    1. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;181(2):281–92.e6. 10.1016/j.cell.2020.02.058 - DOI - PMC - PubMed
    1. Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science. 2020:eabb9983. - PMC - PubMed

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