Evidence map›Paper›PMID 19553314›Full record

ArticleJournal of virology2009

Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells.

Yoshiyuki Yamada, Ding Xiang Liu

Abstract read
In one paragraph

Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

112 citing papers in PubMed, 183 citations in OpenAlex.

  1. Article
  2. TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026
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52 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

2 authors at 2 institutions in 1 country.

Yoshiyuki YamadaInstitute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.
Ding Xiang Liu
Institute of Molecular and Cell Biology · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The spike (S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR(537)/S in virus-infected cells. In this study, we observe that the S2 subunit of the IBV Beaudette strain is additionally cleaved at the second furin site (RRRR(690)/S) in cells expressing S constructs and in virus-infected cells. Detailed time course experiments showed that a peptide furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, blocked both viral entry and syncytium formation. Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry. Instead, a yet-to-be-identified serine protease(s) was involved, as revealed by protease inhibitor studies. Furthermore, sequence analysis of CoV S proteins by multiple alignments showed conservation of an XXXR/S motif, cleavable by either furin or other trypsin-like proteases, at a position equivalent to the second IBV furin site. Taken together, these results suggest that proteolysis at a novel XXXR/S motif in the S2 subunit might be a common mechanism for the entry of CoV into cells.

Indexed as

Cell FusionVirus InternalizationAmino Acid MotifsAmino Acid SubstitutionAnimalsChlorocebus aethiopsFurinGiant CellsInfectious bronchitis virusMembrane GlycoproteinsMutagenesis, Site-DirectedSpike Glycoprotein, CoronavirusVero CellsViral Envelope ProteinsFurinMembrane GlycoproteinsSpike Glycoprotein, Coronavirusspike glycoprotein, SARS-CoVspike protein, mouse hepatitis virusViral Envelope Proteins

Identifiers

PMID19553314
PMCPMC2738192
OpenAlexW2167490988

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.