Evidence map›Paper›PMID 33310888›Full record

ArticleJournal of virology2021

Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects.

Hanh T Nguyen, Shijian Zhang, Qian Wang, Saumya Anang, Jia Wang, Haitao Ding, John C Kappes, Joseph Sodroski

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 7% 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

66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Characteristics of Oral Adverse Effects following COVID-19 Vaccination and Similarities with Oral Symptoms in COVID-19 Patients: Taste and Saliva Secretory Disorders.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. Palmitoylation at a conserved cysteine residue facilitates gasdermin D-mediated pyroptosis and cytokine release.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Inconspicuous Yet Indispensable: The Coronavirus Spike Transmembrane Domain.International journal of molecular sciences · 2023
    Review
  18. Review
  19. Review
  20. Review

6 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Hanh T NguyenDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Shijian ZhangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Qian WangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Saumya AnangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jia WangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Haitao DingDepartment of Medicine, University of Alabama at Birmingham, AL 35294, USA.
John C KappesDepartment of Medicine, University of Alabama at Birmingham, AL 35294, USA.
Joseph SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA joseph_sodroski@dfci.harvard.edu.ORCID https://orcid.org/0000-0002-9750-1615
Harvard University · USUniversity of Alabama at Birmingham · US

Funding

Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
Conformational Landscape of the HIV-1 Envelope GlycoproteinsR01AI124982 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2016 to 2025
$6.7M
Enrichment of the State-1 Conformation of the HIV-1 Envelope GlycoproteinR01AI145547 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2019 to 2021
$2.2M
NIAID NIH HHS P30 AI027767NIAID NIH HHS R01 AI124982NIAID NIH HHS R01 AI145547
6 · The paper itself

Abstract

SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects (syncytium formation). We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced syncytium-forming ability. Notably, the D614G change found in globally predominant SARS-CoV-2 strains increased infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, these two features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both host proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.

Identifiers

PMID33310888
PMCPMC8092844
OpenAlexW3112772443

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.