Map of SARS-CoV-2 spike epitopes not shielded by glycans

Sikora, Mateusz; Bülow, Sören von; Blanc, Florian; Gecht, Michael; Covino, Roberto; Hummer, Gerhard

doi:10.1101/2020.07.03.186825

Cited by 29 publications

(47 citation statements)

References 60 publications

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“…(23,37,38) To this end, we have performed MD simulations of fully glycosylated spike protein of SARS-COV-2 in both open and closed states. Analysis of dynamics for 1 μs trajectories showed a tilting motion in the stalk region, which was also demonstrated with experimental cryo-ET images (29,30) and suggested to aid the virus with screening the host cells for receptor proteins (Figure 2A). Glycan motions were characterized by RMSF ( Figures 2B and S3), which showed higher values for stalk glycans demonstrating the high shielding potential of this normally solvent-exposed region.…”

Section: Discussionsupporting

confidence: 65%

Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2

Ghorbani

Brooks

Klauda

2020

Preprint

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The ongoing pandemic caused by coronavirus SARS-COV-2 continues to rage with devastating consequences on human health and global economy. The spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all current antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein, we performed microsecond-long MD simulation in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the spike trimer. Role of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis, where the high betweenness centrality of glycans at the apex revealed their importance and function in the glycan shield. Microdomains of glycans were identified featuring a high degree of intra-communication in these microdomains. An antibody overlap analysis revealed the glycan microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Overall, the results of this study provide detailed understanding of the spike glycan shield, which may be utilized for therapeutic efforts against this crisis.

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Section: Discussionsupporting

confidence: 65%

Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2

Ghorbani

Brooks

Klauda

2020

Preprint

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“…DC-SIGN and L-SIGN have been already described as receptor of SARS-CoV-1 and twenty out of the twenty-two SARS-CoV-2 S protein N-linked glycosylation sequons are conserved. Glycan shielding represent 60 to 90 % of the spike surface considering the head or the stalk of the S ectodomain, respectively (Casalino et al, 2020;Sikora et al, 2020). One third of N-glycans of SARS-CoV-2 spike are of the oligomannose type (Watanabe et al, 2020a).…”

Section: Several C-type Lectin Receptors Can Interact With Sars-cov-2mentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

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The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis.

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“…Insights into the sequences mutations of S protein among available genomes on the GISAID database, we found three principal variations, H49Y, D614G, and T573I in the Mexican population. The 3D crystal structures of S protein are available at PDB database 2,[15][16][17] . However, to capture conformational changes in the 3D atomistic model, Molecular Dynamic simulation (MD) needs to be performed 15 .…”

Section: Introductionmentioning

confidence: 99%

“…The 3D crystal structures of S protein are available at PDB database 2,[15][16][17] . However, to capture conformational changes in the 3D atomistic model, Molecular Dynamic simulation (MD) needs to be performed 15 . To determine if the variants H49Y, D614G, and T573I on S protein founded on the Mexican population, could affect the 3D structure, here we employed molecular dynamics simulations (MD) for a full-length atomistic 3D structure of S protein and its variants.…”

Section: Introductionmentioning

confidence: 99%

Structural insights into spike protein and its natural variants of SARS-CoV-2 found on Mexican population.

Sixto-López

Bello

Correa-Basurto

et al. 2020

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus responsible for COVID-19; it becomes a pandemic since March 2020. To date, there are described three lineages of SARS-CoV-2 circulating worldwide, in Mexican population are found two of them, within this, we observed three variants of Spike (S) protein located at H49Y, D614G, and T573I. In order to understand if these mutations could affect the structural behavior of S protein of SARS-CoV-2, as well as the binding with three experimental describe inhibitors (Cepharanthine, Nelfinavir, and Hydroxychloroquine), molecular dynamic simulation and molecular docking were employed. It was found that in spite, these punctual mutations affect considerably the structural behavior of the S Protein, which also affect the binding of the inhibitors into their respective binding site. Thus, further experimental studies need to be done in order to explore if these affectations have an impact on drug-S protein binding and the possible clinical effect.

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Map of SARS-CoV-2 spike epitopes not shielded by glycans

Cited by 29 publications

References 60 publications

Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2

Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Structural insights into spike protein and its natural variants of SARS-CoV-2 found on Mexican population.

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