Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Wang, Pengfei; Nair, Manoj S.; Liu, Lihong; Iketani, Sho; Luo, Yang; Guo, Yicheng; Wang, Maple; Yu, Jian; Zhang, Baoshan; Kwong, Peter D.; Graham, Barney S.; Mascola, John R.; Chang, Joseph; Yin, Michael T.; Sobieszczyk, Magdalena E.; Kyratsous, Christos A.; Shapiro, Lawrence; Sheng, Zizhang; Huang, Yaoxing; Ho, David D.

doi:10.1038/s41586-021-03398-2

“…Two most recent studies have mapped the immune epitopes recognized by the antibodies in humans. These are consistent with the assumption that monoclonal antibodies and convalescent sera against the SARS-CoV-2 Wuhan isolate bind to a surface area distinctly different from the surface patch surrounding His69 of the SARS-CoV-2 S-protein (49,50), the putative glycan binding pocket. Previous analyses in genetics have supported the role of glycans in the susceptibility of the human population to SARS-CoV-1 and -2 infection and/or severity of disease (COVID-19).…”

Section: Discussionsupporting

confidence: 88%

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

Fiedler¹

2021

Preprint

0

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The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

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“…Two most recent studies have mapped the immune epitopes recognized by the antibodies in humans. These are consistent with the assumption that monoclonal antibodies and convalescent sera against the SARS-CoV-2 Wuhan isolate bind to a surface area distinctly different from the surface patch surrounding His69 of the SARS-CoV-2 S-protein (48,49), the putative glycan binding pocket. Previous analyses in genetics have supported the role of glycans in the susceptibility of the human population to SARS-CoV-1 and -2 infection and/or severity of disease (COVID-19).…”

Section: Discussionsupporting

confidence: 88%

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

Fiedler¹

2021

Preprint

0

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

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“…For example, the B.1.1.7 variant contains spike protein mutations D614G and N501Y that have been reported to increase transmission and to subsequently cause a more severe COVID-19 manifestation with increased hospitalization and mortality rates (Davies et al, 2021;Hou et al, 2020;Korber et al, 2020;Rambaut et al, 2020). Moreover, both the B.1.1.7 and B.1.351 variants contain extensive mutations in the spike protein that cause increased resistance to neutralization by antibodies derived from convalescent patients' plasma and vacinee sera (Wang et al, 2021). The potential public health challenges posed by these emerging VOCs warrant extensive real-time surveillance at the community level to inform efforts in controlling the pandemic (CDC, 2020).…”

Section: Introductionmentioning

confidence: 99%

Quantitative detection of SARS-CoV-2 B.1.1.7 variant in wastewater by allele-specific RT-qPCR

Lee

¹

,

McElroy²,

Armas

³

et al. 2021

Preprint

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Wastewater-based epidemiology (WBE) has emerged as a critical public health tool in tracking the SARS-CoV-2 epidemic. Monitoring SARS-CoV-2 variants of concern in wastewater has to-date relied on genomic sequencing, which lacks sensitivity necessary to detect low variant abundances in diluted and mixed wastewater samples. Here, we develop and present an open-source method based on allele specific RT-qPCR (AS RT-qPCR) that detects and quantifies the B.1.1.7 variant, targeting spike protein mutations at three independent genomic loci highly predictive of B.1.1.7 (HV69/70del, Y144del, and A570D). Our assays can reliably detect and quantify low levels of B.1.1.7 with low cross-reactivity, and at variant proportions between 0.1% and 1% in a background of mixed SARS-CoV-2. Applying our method to wastewater samples from the United States, we track B.1.1.7 occurrence over time in 19 communities. AS RT-qPCR results align with clinical trends, and summation of B.1.1.7 and wild-type sequences quantified by our assays strongly correlate with SARS-CoV-2 levels indicated by the US CDC N1/N2 assay. This work paves the path for rapid inexpensive surveillance of B.1.1.7 and other SARS-CoV-2 variants in wastewater.

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Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Cited by 2,025 publications

References 46 publications

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

Quantitative detection of SARS-CoV-2 B.1.1.7 variant in wastewater by allele-specific RT-qPCR

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