Evidence map›Paper›PMID 40492735›Full record

ArticleJournal of virology2025

The furin cleavage site is required for pathogenesis, but not transmission, of SARS-CoV-2.

Angelica L Morgan, Michelle N Vu, Yiyang Zhou, Kumari G Lokugamage, William M Meyers, R Elias Alvarado, Yani Ahearn, Leah K Estes, Jessica A Plante, Bryan A Johnson and 4 more

Abstract read
In one paragraph

Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
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  5. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Angelica L Morgan *Experimental Pathology Graduate Program, University of Texas Medical Branch, Galveston, Texas, USA.
Michelle N Vu *Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Yiyang ZhouDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Kumari G LokugamageDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
William M MeyersExperimental Pathology Graduate Program, University of Texas Medical Branch, Galveston, Texas, USA.
R Elias AlvaradoDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Yani AhearnDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Leah K EstesDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Jessica A PlanteDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Bryan A JohnsonDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.ORCID 0000-0002-8999-1255
Mehul S SutharDepartment of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
David H WalkerInstitute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, Texas, USA.
Ken S PlanteDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Vineet D MenacheryDepartment of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA.ORCID 0000-0001-8803-7606

Funding

World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)R24AI120942 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI WEAVER, SCOTT C · 2016 to 2024
$8.5M
Biodefense Training ProgramT32AI060549 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI ASHOK K CHOPRA, Janice J Endsley · 2004 to 2026
$3.0M
RNA Recombination in CoronavirusesR01AI168232 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI VINEET D MENACHERY, Andrew Laurence Routh · 2023 to 2026
$2.1M
Identifying host and viral correlates for coronavirus pathogenesisR01AI153602 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI JOHNSON, BRYAN A · 2020 to 2023
$2.0M
NIAID NIH HHS R01 AI153602NIAID NIH HHS R01 AI168232NIAID NIH HHS R24 AI120942NIAID NIH HHS T32 AI060549
6 · The paper itself

Abstract

The SARS-CoV-2 spike, key to viral entry, has two features that differentiate it from other sarbecoviruses: the presence of a furin cleavage site (FCS; PRRAR sequence) and an extended S1/S2 loop characterized by an upstream QTQTN amino acid motif. Our prior works show that shortening the S1/S2 loop by deleting either the FCS (ΔPRRA) or an upstream sequence (ΔQTQTN) ablates spike processing, alters host protease usage, and attenuates infection IMPORTANCE: The presence of the furin cleavage site (FCS) within the spike protein of SARS-CoV-2 distinguishes it from other sarbecoviruses found in nature. While prior works have deleted the FCS, these mutant viruses also shortened the S1/S2 loop, which is known to be important for pathogenesis. This study defines the importance of the FCS in the context of the extended SARS-CoV-2 S1/S2 loop. The study finds that the FCS disruption mutant is attenuated

Indexed as

COVID-19FurinSARS-CoV-2Spike Glycoprotein, CoronavirusAnimalsChlorocebus aethiopsHumansMiceMutationVero CellsVirus InternalizationVirus ReplicationFurinFURIN protein, humanSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2entryfurin cleavage siteproteaseQTQTNS1/S2 LoopSARS-CoV-2spike

Identifiers

PMID40492735
PMCPMC12282137

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.