Evidence mapPaperPMID 40703349Full record

ArticleFrontiers in pharmacology2025

The GPR4 antagonist NE-52-QQ57 increases survival, mitigates the hyperinflammatory response and reduces viral load in SARS-CoV-2-infected K18-hACE2 transgenic mice.

Xin-Jun Wu, Karen A Oppelt, Ming Fan, Mona A Marie, Madison M Swyers, Ashley J Williams, Isabelle M Lemasson, Rachel L Roper, Paul Bolin, Li V Yang

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Xin-Jun WuDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Karen A OppeltDepartment of Comparative Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Ming FanDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Mona A MarieDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Madison M SwyersDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Ashley J WilliamsDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Isabelle M LemassonDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Rachel L RoperDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Paul BolinDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Li V YangDepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

COVID-19 (Coronavirus disease 19) is caused by infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the respiratory system and other organ systems. Tissue injuries resulting from viral infection and host hyperinflammatory responses may lead to moderate to severe pneumonia, systemic complications, and even death. While anti-inflammatory agents have been used to treat patients with severe COVID-19, their therapeutic effects are limited. GPR4 (G protein-coupled receptor 4) is a pro-inflammatory receptor expressed on vascular endothelial cells, regulating leukocyte infiltration and inflammatory responses. In this study, we evaluated the effects of a GPR4 antagonist, NE-52-QQ57, in the SARS-CoV-2-infected K18-hACE2 transgenic mouse model. Our results demonstrated that GPR4 antagonist treatment increased the survival rate in this severe COVID-19 mouse model. The inflammatory response, characterized by proinflammatory cytokines and chemokines, was reduced in the GPR4 antagonist group compared with the vehicle group. Additionally, both SARS-CoV-2 RNA copy numbers and infectious viral titers in the mouse lung were decreased in the GPR4 antagonist group. The percentage of SARS-CoV-2 antigen-positive mouse brains was also decreased in the GPR4 antagonist group compared to the vehicle group. Furthermore, the GPR4 antagonist inhibited SARS-CoV-2 propagation in Vero E6 and Caco-2 cells. Together, these results suggest that GPR4 antagonism may be explored as a novel approach for the treatment of COVID-19 and other similar viral diseases.

Indexed as

anti-inflammationantiviralCOVID-19GPR4 antagonistmouse modelSARS-CoV-2

Identifiers

PMID40703349
PMCPMC12283652

What Socratic holds

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Registered trials

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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 Socratic graph.