Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

Walls, Alexandra C.; Xiong, Xiaoli; Park, Young‐Jun; Tortorici, M. Alejandra; Snijder, Joost; Quispe, Joel; Cameroni, Elisabetta; Gopal, Robin; Dai, Mian; Lanzavecchia, Antonio; Zambon, Maria; Rey, F.A.; Corti, Davide; Veesler, David

doi:10.1016/j.cell.2018.12.028

Cell

2019

DOI: 10.1016/j.cell.2018.12.028

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Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

Alexandra C. Walls

¹

,

Xiaoli Xiong

²

,

Young‐Jun Park

³

et al.

Abstract: Graphical Abstract Highlights d MERS-CoV/SARS-CoV S composite glycan shields analyzed by cryo-EM and mass spectrometry d Structures of MERS-CoV/SARS-CoV S with neutralizing antibodies from survivors d LCA60 inhibits receptor binding by interacting with MERS-CoV S protein/glycans d S230 blocks receptor binding and triggers fusogenic rearrangements via functional mimicry In Brief Structural analysis of the SARS-CoV S and MERS-CoV S glycoproteins in complex with neutralizing antibodies from human survivors sheds … Show more

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Cited by 692 publications

(910 citation statements)

References 87 publications

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“…4b, c ). This finding is congruent with previous studies investigating S230 escape mutants, demonstrating that residue L443 in SARS-CoV S is central and key for S230 binding [ 53 ]. An alignment of SARS-CoV and SARS-CoV 2 RBDs revealed this residue to be divergent between the two coronaviruses, resulting in reduced S230 binding and functionality ( Fig.…”

Section: Resultssupporting

confidence: 92%

Micro-fusion inhibition tests: quantifying antibody neutralization of virus-mediated cell–cell fusion

Thakur

¹

,

Conceicao

²

,

Isaacs

³

et al. 2021

Journal of General Virology

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…4b, c ). This finding is congruent with previous studies investigating S230 escape mutants, demonstrating that residue L443 in SARS-CoV S is central and key for S230 binding [ 53 ]. An alignment of SARS-CoV and SARS-CoV 2 RBDs revealed this residue to be divergent between the two coronaviruses, resulting in reduced S230 binding and functionality ( Fig.…”

Section: Resultssupporting

confidence: 92%

Micro-fusion inhibition tests: quantifying antibody neutralization of virus-mediated cell–cell fusion

Thakur

¹

,

Conceicao

²

,

Isaacs

³

et al. 2021

Journal of General Virology

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…It is also interesting to note that the distribution of oligomannose-type glycans was broad, with Man 5 GlcNAc 2 to Man 9 GlcNAc 2 glycans all present, without one particular dominant peak, as is the case for some viral glycoproteins, such as HIV-1 Env 36 . The proportion of oligomannose-type glycans on recombinant coronavirus S proteins is consistent with previous studies performed on virally derived MERS and SARS coronavirus S proteins 17,42 . Coronaviruses have been previously been reported to form virions by budding into the lumen of endoplasmic reticulum-Golgi intermediate compartments (ERGIC) 43,44 .…”

Section: Resultssupporting

confidence: 91%

Vulnerabilities in coronavirus glycan shields despite extensive glycosylation

Watanabe

¹

,

Berndsen

²

,

Raghwani

³

et al. 2020

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…Only one glycosite (603) was of the high-mannose-type. Our study is consistent with the previous study on SARS-CoV S protein, in which Walls et al revealed that the complex N-glycans rather than oligomannose-types were linked to the preserved glycosites (61, 122, 603, 709, 801, and 1074) between SARS-CoV S and SARS-CoV-2 ( 5 ). In contrast, we found that the insect cell-expressed S protein contained 38 N-glycans, comprising entirely the high-mannose-type.…”

Section: Discussionsupporting

confidence: 93%

“…S8-9 , Table S7 ). Our findings are in line with those of previous studies, that demonstrated the predominant complex of N-glycans attached to MERS-CoV and SARS-CoV proteins ( 4 , 5 , 35 ). Moreover, two recent studies by Watanabe et al and Shajahan et al have revealed that the complex N-glycans dominate the glycosites on human cell-expressed SARS-CoV-2 S protein( 17 , 18 ).…”

Section: Discussionsupporting

confidence: 93%

Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins

Zhang

¹

,

Zhao

²

,

Mao

³

et al. 2021

Molecular & Cellular Proteomics

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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