Impact of glycan cloud on the B-cell epitope prediction of SARS-CoV-2 Spike protein

Abstract

The SARS-CoV-2 outbreak originated in China in late 2019 and has since spread to pandemic proportions. Diagnostics, therapeutics and vaccines are urgently needed. We model the trimeric Spike protein, including flexible loops and all N-glycosylation sites, in order to elucidate accessible epitopes for antibody-based diagnostics, therapeutics and vaccine development. Based on published experimental data, six homogeneous glycosylation patterns and two heterogeneous ones were used for the analysis. The glycan chains alter the accessible surface areas on the S-protein, impeding antibody-antigen recognition. In presence of glycan, epitopes on the S1 subunit, that notably contains the receptor binding domain, remain mostly accessible to antibodies while those present on the S2 subunit are predominantly inaccessible. We identify 28 B-cell epitopes in the Spike structure and group them as nonaffected by the glycan cloud versus those which are strongly masked by the glycan cloud, resulting in a list of favourable epitopes as targets for vaccine development, antibody-based therapy and diagnostics.

Complement control for COVID-19

“…Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, 02118, MA, USA 2. Center for Thrombosis and Hemostasis, University Medical Center Mainz, 55131 Mainz, Germany 3. Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, 02118, USA 4.…”

The evolutionary making of SARS-CoV-2

“…However, the spike protein is heavily glycosylated, and the glycans shield a considerable fraction of the protein from interactions with host molecules (Casalino, et al 2020; Sikora, et al 2020; Watanabe, et al 2020; Wintjens, et al 2020; Yang, et al 2020). Since structural information was not considered in the prediction procedure, we integrated the position of the 9 epitopes with surface-accessibility information from a recent structural and physics-based modeling approach (Sikora, et al 2020).…”

“…The four epitopes located in the RBD (LE2,4-6), which establishes the connection to ACE2, are of particular interest. Three of them (LE2,5,6) overlap with predicted B-cell epitopes that are at most partly shielded by glycans (Wintjens, et al 2020). LEs 2 and 4, which correspond to the N- and C-termini of the RBD are present in almost all sarbecoviruses.…”

Rarely Recognized Antibody Diversification in Covid-19 Evolution to Counteract Advanced SARS-CoV-2 Evasion Strategies, and Implications for Prophylactic Treatment

“…It is unknown whether convalescent sera of SARS-CoV-2 individuals recognize the "glycan cloud." Wintjens et al, 2020 Glycosylation sites are under selective pressure to facilitate immune evasion by shielding of specific epitopes. Watanabe et al, 2020 Glycans obstruct receptor binding and proteolytic processing during antigen presentation and alter the accessible surface areas on the S-protein, impeding antibody-antigen recognition.…”

“…Watanabe et al, 2020 Glycans obstruct receptor binding and proteolytic processing during antigen presentation and alter the accessible surface areas on the S-protein, impeding antibody-antigen recognition. Wintjens et al, 2020;Zhang et al, 2020 The glycan masking of epitopes may address why some patients' sera is limited in its ability to prevent virus entry into host cells. Walls et al, 2020;Wintjens et al, 2020 Viral mutants may evade host antibodies without changing the epitope sequence, but rather by changing the glycan chain orientation.…”