Evidence map›Paper›PMID 34540146›Full record

ArticleComputational and structural biotechnology journal2021

Computational insights into the membrane fusion mechanism of SARS-CoV-2 at the cellular level.

Jimin Wang, Federica Maschietto, Matthew J Guberman-Pfeffer, Krystle Reiss, Brandon Allen, Yong Xiong, Elias Lolis, Victor S Batista

Open access · goldAbstract read
In one paragraph

Article in Computational and structural biotechnology journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Multifaceted membrane binding head of the SARS-CoV-2 spike protein.Current research in structural biology · 2022
    Article
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 1 institution in 1 country.

Jimin WangDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, United States.
Federica MaschiettoDepartment of Chemistry, Yale University, New Haven, CT 06511-8499, United States.
Matthew J Guberman-PfefferDepartment of Chemistry, Yale University, New Haven, CT 06511-8499, United States.
Krystle ReissDepartment of Chemistry, Yale University, New Haven, CT 06511-8499, United States.
Brandon AllenDepartment of Chemistry, Yale University, New Haven, CT 06511-8499, United States.
Yong XiongDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, United States.
Elias LolisDepartment of Pharmacology, Yale University, New Haven, CT 06520-8066, United States.
Victor S BatistaDepartment of Chemistry, Yale University, New Haven, CT 06511-8499, United States.
Yale University · US

Funding

PREDOCTORAL PROGRAM IN BIOPHYSICST32GM008283 · NIGMS · YALE UNIVERSITY · PI XIONG, YONG · 1988 to 2022
$10.5M
Computational and Biochemical Studies of Temperature Effects on Allostery in the Imidazole Glycerol Phosphate Synthase (IGPS) from T. maritimaR01GM106121 · NIGMS · YALE UNIVERSITY · PI BATISTA, VICTOR S, LORIA, JOSEPH P · 2014 to 2021
$2.3M
NIGMS NIH HHS R01 GM106121
6 · The paper itself

Abstract

The membrane fusion mechanism of SARS-CoV-2 offers an attractive target for the development of small molecule antiviral inhibitors. Fusion involves an initial binding of the crown-like trimeric spike glycoproteins of SARS-CoV-2 to the receptor angiotensin II-converting enzyme 2 (ACE2) on the permissive host cellular membrane and a prefusion to post-fusion conversion of the spike trimer. During this conversion, the fusion peptides of the spike trimer are inserted into the host membrane to bring together the host and viral membranes for membrane fusion in highly choreographic events. However, geometric constraints due to interactions with the membranes remain poorly understood. In this study, we build structural models of super-complexes of spike trimer/ACE2 dimers based on the molecular structures of the ACE2/neutral amino acid transporter B(0)AT heterodimer. We determine the conformational constraints due to the membrane geometry on the enzymatic activity of ACE2 and on the viral fusion process. Furthermore, we find that binding three ACE2 dimers per spike trimer is essential to open the central pore as necessary for triggering productive membrane fusion through an elongation of the central stalk. The reported findings thus provide valuable insights for targeting the membrane fusion mechanism for drug design at the molecular level.

Indexed as

ACE2 dimerPeptidase domainPost-fusion conformationPrefusion conformationSARS-CoV2Spike trimersSuper-complex

Identifiers

PMID34540146
PMCPMC8442599
OpenAlexW3197490556

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.