Evidence map›Paper›PMID 40577599›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.

Yao Tong, Travis B Lear, Ferhan Tuncer, John J Villandre, Áine N Boudreau, Bo Lin, Irene Alfaras, Jason R Kennerdell, Daniel P Camarco, Mads B Larsen and 9 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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

19 authors.

Yao TongAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.ORCID 0000-0001-6573-859X
Travis B LearAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Ferhan TuncerAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
John J VillandreAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Áine N BoudreauAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Bo LinAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Irene AlfarasAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Jason R KennerdellAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Daniel P CamarcoAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Mads B LarsenAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Yun HuaAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Yanwen ChenAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Meigin E ChandlerAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Ricardo PinedaDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Simon M Barratt-BoyesDepartment of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
John W EvankovichAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Toren FinkelAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Yuan LiuAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.
Bill B ChenAging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, 15219, USA.ORCID 0000-0003-2695-5107

Funding

VARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JENNIFER S BRACH · 2004 to 2026
$28.6M
TriState SenNET (Lung and Heart) Tissue Map and Atlas consortiumU54AG075931 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TOREN FINKEL, Melanie Koenigshoff · 2021 to 2026
$14.0M
Developing a NAMPT activator for Alzheimer’s diseaseU01AG079828 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Beibei Chen, Stacey J Rizzo · 2023 to 2026
$9.4M
Systematic Investigation of Protein Ubiquitination in ARDSR35HL139860 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, BEIBEI · 2018 to 2024
$6.3M
Translational Pulmonary Vascular BiologyT32HL110849 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sruti Shiva · 2012 to 2026
$5.0M
Host Defense Small Molecule Development for COVID-19 Treatment by Targeting LysosomeR01AI172935 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Simon M Barratt-Boyes, Yuan Liu · 2023 to 2026
$3.1M
DCAF7/HDAC4/TFEB axis in acute lung injuryR01HL142777 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LIU, YUAN · 2018 to 2022
$2.4M
Degradation of Toll-Like Receptor 8 by RNF216 in response to plasma MicroRNA’s – A Novel Mechanism Regulating Inflammation in Acute Lung InjuryK08HL144820 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI EVANKOVICH, JOHN W · 2019 to 2023
$810k
Modulating Alzheimer's Disease by mTORC1 inhibition to augment lysosomal activityR00AG078342 · NIA · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Travis Bradley Lear · 2025 to 2026
$493k
Modulating Alzheimer’s Disease by mTORC1 inhibition to augment lysosomal activityK99AG078342 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEAR, TRAVIS BRADLEY · 2022 to 2023
$245k
American Heart Association 24SFRNPCN1280227Foundation for the National Institutes of Health AI172935Hevolution Foundation HF-GRO-23-1199160-9Jewish Healthcare FoundationNHLBI NIH HHS K08 HL144820NHLBI NIH HHS R01 HL142777NHLBI NIH HHS R35 HL139860NHLBI NIH HHS T32 HL110849NIAID NIH HHS R01 AI172935NIA NIH HHS K99 AG078342NIA NIH HHS P30 AG024827NIA NIH HHS R00 AG078342NIA NIH HHS U01 AG079828NIA NIH HHS U54 AG075931University of Pittsburgh Aging Institute Seed Fund
6 · The paper itself

Abstract

NSP7 (Non-Structural Protein 7) of SARS-CoV-2 is a crucial component for viral replication and transcription. In this study, it is revealed that the host E3 ubiquitin ligase FBXO5 suppresses viral replication by mediating NSP7 lysine-48-linked ubiquitination and subsequent proteasomal degradation. Interestingly, it is also determined that NSP7 expression impairs the host antiviral response by inhibiting the ISGylation of melanoma differentiation-associated protein 5 (MDA5), a key sensor for viral RNA. Through an unbiased esiRNA screen, it is identified that NSP7 ubiquitination is coregulated by β-TrCP1 and the kinase TAF1. Additionally, this study uncovers a small molecule FBXO5 stabilizer that disrupts the β-TrCP1-FBXO5 interaction, thereby markedly enhancing NSP7 degradation and effectively mitigating SARS-CoV-2 infection. Taken together, the findings reveal a novel mechanism for NSP7 regulation and suggest that small-molecule activators of the E3 ubiquitin ligase FBXO5 represent a promising new class of host-directed antiviral therapies.

Indexed as

beta-Transducin Repeat-Containing ProteinsCOVID-19F-Box ProteinsSARS-CoV-2Viral Nonstructural ProteinsHEK293 CellsHumansUbiquitinationUbiquitin-Protein LigasesVirus Replicationbeta-Transducin Repeat-Containing ProteinsBTRC protein, humanF-Box ProteinsUbiquitin-Protein LigasesViral Nonstructural Proteinsantiviral therapiesFBXO5non‐structural protein 7TAF1ubiquitinationβ‐TrCP1

Identifiers

PMID40577599
PMCPMC12463105

What OpenQuestion holds

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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.