Evidence map›Paper›PMID 34004056›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021

Disruption of disulfides within RBD of SARS-CoV-2 spike protein prevents fusion and represents a target for viral entry inhibition by registered drugs.

Mateja Manček-Keber, Iva Hafner-Bratkovič, Duško Lainšček, Mojca Benčina, Tea Govednik, Sara Orehek, Tjaša Plaper, Vid Jazbec, Valter Bergant, Vincent Grass and 2 more

Open access · hybridAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Machine learning-guided rational engineering of ACE2-derived peptides for broad-spectrum neutralization of SARS-CoV-2 variants.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
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  14. Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022
    Review
  15. Review
  16. Utility of NO and HNitric oxide : biology and chemistry · 2022
    Review
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  20. The Effects of HBiomedicines · 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

12 authors at 3 institutions in 4 countries.

Mateja Manček-KeberDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID https://orcid.org/0000-0003-4976-8857
Iva Hafner-BratkovičDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID https://orcid.org/0000-0001-5635-931X
Duško LainščekDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Mojca BenčinaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Tea GovednikDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Sara OrehekDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Tjaša PlaperDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Vid JazbecDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Valter BergantImmunopathology of Virus Infections Laboratory, Institute of Virology, Technical University of Munich, Munich, Germany.
Vincent GrassImmunopathology of Virus Infections Laboratory, Institute of Virology, Technical University of Munich, Munich, Germany.
Andreas PichlmairImmunopathology of Virus Infections Laboratory, Institute of Virology, Technical University of Munich, Munich, Germany.
Roman JeralaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
EN-FIST Centre of Excellence (Slovenia) · SIUniversity of Ljubljana · SIDepartment of Virology · FR

Funding

Slovenian Research Agency J3-9257Slovenian Research Agency P4-0176Slovenian Research Agency V4-2038
6 · The paper itself

Abstract

The SARS-CoV-2 pandemic imposed a large burden on health and society. Therapeutics targeting different components and processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines and therapeutics. Insights into the mechanisms of spike-ACE2 binding and cell fusion could support the identification of compounds with inhibitory effects. Here, we demonstrate that the integrity of disulfide bonds within the receptor-binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2. Several reducing agents and thiol-reactive compounds are able to inhibit viral entry. N-acetyl cysteine amide, L-ascorbic acid, JTT-705, and auranofin prevented syncytia formation, viral entry into cells, and infection in a mouse model, supporting disulfides of the RBD as a therapeutically relevant target.

Indexed as

COVID-19COVID-19 Drug TreatmentAcetylcysteineAmidesAscorbic AcidAuranofinDisulfidesEstersHEK293 CellsHumansSARS-CoV-2Spike Glycoprotein, CoronavirusSulfhydryl CompoundsVirus InternalizationAcetylcysteineAmidesAscorbic AcidAuranofindalcetrapibDisulfidesEstersN-AcetylcysteinamideSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Sulfhydryl CompoundsACE2disulfidesSARS-CoV-2spikethiol-reacting compounds

Identifiers

PMID34004056
PMCPMC8206760
OpenAlexW3161244103

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.