Evidence map›Paper›PMID 38444370›Full record

ArticleMicrobiology and immunology2024

N-glycosylation of the SARS-CoV-2 spike protein at Asn331 and Asn343 is involved in spike-ACE2 binding, virus entry, and regulation of IL-6.

Tuhin Das, Shuhong Luo, Hao Tang, Jianmin Fang, Yinging Mao, Haw-Han Yen, Sabyasachi Dash, Asif Shajahan, Lauren Pepi, Steven Huang and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Microbiology and immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 2 countries.

Tuhin DasRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0001-8202-0838
Shuhong LuoRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0002-9058-4833
Hao TangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Jianmin FangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Yinging MaoRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0009-0004-2193-7983
Haw-Han YenRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Sabyasachi DashDepartment of Pathology, Center for Vascular Biology, Weill Cornell Medicine, New York, New York, USA.ORCID http://orcid.org/0000-0003-3966-9396
Asif ShajahanVaccine Research Center, Gaithersburg, Maryland, USA.ORCID http://orcid.org/0000-0002-4804-1130
Lauren PepiVaccine Research Center, Gaithersburg, Maryland, USA.ORCID http://orcid.org/0000-0002-5740-4175
Steven HuangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Valerie S JonesRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0002-4204-9959
Shehuo XieRayBiotech Guangzhou Co. Ltd. Guangzhou, Guangzhou, China.
Gordon F HuangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Jinqiao LuRayBiotech Life Inc., Peachtree Corners, Georgia, USA.
Blake AndersonRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0003-3237-9046
Benyue ZhangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0002-3610-3517
Parastoo AzadiComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.ORCID http://orcid.org/0000-0002-6166-9432
Ruo-Pan HuangRayBiotech Life Inc., Peachtree Corners, Georgia, USA.ORCID http://orcid.org/0000-0002-5884-8026
RayBiotech (United States) · USRayBiotech (China) · CNCornell University · USUniversity of Georgia · US

Funding

National Glycoscience Resource- CCRC Service and Training - NGlycoR@CCRCR24GM137782 · NIGMS · UNIVERSITY OF GEORGIA · PI Parastoo Azadi · 2020 to 2026
$5.2M
National Institutes of Health (NIH) R24GM137782-01NIGMS NIH HHS R24 GM137782
6 · The paper itself

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global public health crisis. The causative agent, the SARS-CoV-2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS-CoV-2 spike protein is extensively decorated with up to 66 N-linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N-glycosylation at Asn331 and Asn343 of SARS-CoV-2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS-CoV-2 spike protein into cells. Interestingly, high-content glycan binding screening data have shown that N-glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galβ-1,4 GlcNAc), which is critical for spike-RBD-ACE2 binding. Furthermore, IL-6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N-glycosylation of Asn331 and Asn343 sites of the spike receptor-binding domain (RBD) significantly reduced the transcriptional upregulation of pro-inflammatory signaling molecule IL-6. In addition, IL-6 levels correlated with spike protein levels in COVID-19 patients' serum. These findings establish the importance of RBD glycosylation in SARS-CoV-2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID-19.

Indexed as

Angiotensin-Converting Enzyme 2COVID-19Interleukin-6Protein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationAsparagineGlycosylationHEK293 CellsHumansPolysaccharidesACE2 protein, humanAngiotensin-Converting Enzyme 2AsparagineIL6 protein, humanInterleukin-6PolysaccharidesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ACE2COVID‐19IL‐6N‐glycosylationreceptor‐binding domainSARS‐CoV‐2spike protein

Identifiers

PMID38444370
PMCPMC11273356
OpenAlexW4392516516

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.