ArticleAntiviral research2023
Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier.
Article in Antiviral research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
The trial behind it
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Stereoretentive Nucleophilic Aromatic Substitution Accesses Atropisomeric 4-Amino-N-Arylquinolinium Salts.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Mesenchymal stem cell derived exosomes mitigate COVID-19 cytokine storm via Annexin A1 and TGF-β mediated MAPK pathway inhibition.Stem cell research & therapy · 2026Article
- Mitogen-Activated Protein Kinases: Therapeutic Signaling Catalysts in Viral Immune Evasion.Pathogens (Basel, Switzerland) · 2026Review
- Review
- Article
- Role of Atypical MAPK p38 Signaling in the Progression of Influenza A-Induced Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Online Conference "Chronic Viral Infections and Cancer, Openings for Vaccines and Cure" VIRCAN2024, Monitoring the Progress.Vaccines · 2025Article
- The MAPK Response to Virus Infection Is Modified by Probenecid.Current issues in molecular biology · 2025Review
- Intersection of inflammation and viral replication: the central role of MAPK signaling in viral respiratory infections.Frontiers in microbiology · 2025Review
- Molecular characterisation of influenza B virus from the 2017/18 season in primary models of the human lung reveals improved adaptation to the lower respiratory tract.Emerging microbes & infections · 2024Article
- Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.Inflammopharmacology · 2024Review
- Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.Cell communication and signaling : CCS · 2024Review
- Comparable Efficacy of Lopinavir/Ritonavir and Remdesivir in Reducing Viral Load and Shedding Duration in Patients with COVID-19.Microorganisms · 2024Article
- Repression of mRNA translation initiation by GIGYF1 via disrupting the eIF3-eIF4G1 interaction.Science advances · 2024Article
- Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models.Zoological research · 2024Review
- Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies.Heliyon · 2024Review
- MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection.Frontiers in immunology · 2024Article
- VX-702 Ameliorates the Severity of Sepsis-Associated Acute Kidney Injury by Downregulating Inflammatory Factors in Macrophages.Journal of inflammation research · 2024Article
- The Function of ASK1 in Sepsis and Stress-Induced Disorders.International journal of molecular sciences · 2023Review
- Large-Scale Biomedical Relation Extraction Across Diverse Relation Types: Model Development and Usability Study on COVID-19.Journal of medical Internet research · 2023Article
Corrections and comments
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Authors and funding
29 authors at 10 institutions in 2 countries.
Funding
Abstract
SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate that targeting p38 signal transduction with the selective and clinically pre-evaluated inhibitors PH-797804 and VX-702 markedly reduced the expression of the pro-inflammatory cytokines IL6, CXCL8, CXCL10 and TNF-α during infection, while viral replication and the interferon-mediated antiviral response of the lung epithelial barrier were largely maintained. Furthermore, our results reveal a high level of drug synergism of both p38 inhibitors in co-treatments with the nucleoside analogs Remdesivir and Molnupiravir to suppress viral replication of the SARS-CoV-2 variants of concern, revealing an exciting and novel mode of synergistic action of p38 inhibition. These results open new avenues for the improvement of the current treatment strategies for COVID-19.
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Registered trials
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.