ArticleJournal of molecular and cellular cardiology2020
p38 MAPK inhibition: A promising therapeutic approach for COVID-19.
Article in Journal of molecular and cellular cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04511819 (A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Losmapimod in Adult Subjects With COVID-19), which is not on this map. Cited by 173 papers, 1 of them a synthesis that pooled it.
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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
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.
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Losmapimod in Adult Subjects With COVID-19 (LOSVID STUDY)
Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Circulating miRNA profiles in COVID-19 patients and meta-analysis: implications for disease progression and prognosis.Scientific reports · 2023Pooled it
- Structure-Guided Design of Proteomimetics Targeting the SARS-CoV-2 S-RBD/hACE2 Interface.Journal of medicinal chemistry · 2026Article
- Designed Liquid Crystalline Nanoassemblies From Clinically Validated Polyunsaturated Lipids for Combined Antioxidant, Anti-Apoptotic, and Neurotrophic Treatments.Advanced healthcare materials · 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
- Rewiring of host cell signaling in chikungunya virus infection: a mechanism for pathogenesis and therapeutic approaches.Archives of microbiology · 2026Review
- Integrated UHPLC-QTOF-MS, Network Pharmacology, and Experimental Validation Reveal the Antiviral and Anti-Inflammatory Mechanisms of Xiaoer Fengreqing Against COVID-19-Associated Encephalitis.Infection and drug resistance · 2026Article
- Molecular Roadmap of COVID-19: From Viral Entry to Therapeutic Targets.Chemistry & biodiversity · 2026Review
- Small Interfering RNA (siRNA) for Cardiorenal Disease: Mechanistic Insights from Preclinical and Clinical Studies.Journal of cardiovascular translational research · 2025Review
- In vitro, in silico, and DFT evaluation of antimicrobial imidazole derivatives with insights into mechanism of action.Scientific reports · 2025Article
- 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
- The potential role of carvedilol in COVID-19 management: perspective and take-away.Inflammopharmacology · 2025Review
- Role for IRAK-4 and p38 in Neutrophil Signaling in Response to Bacterial Lipoproteins from Staphylococcus aureus.Inflammation · 2025Article
- Luteolin-Rich Extract fromLife (Basel, Switzerland) · 2025Article
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2.Journal of medical virology · 2025Article
- Thromboembolic Events in the Era of COVID-19: A Detailed Narrative Review.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Review
- Targeting SIRT1: A Potential Strategy for Combating Severe COVID-19.BioMed research international · 2025Review
- Rethinking Optimal Immunogens to Face SARS-CoV-2 Evolution Through Vaccination.Influenza and other respiratory viruses · 2025Review
- Targeting Ser78 phosphorylation of Hsp27 achieves potent antiviral effects against enterovirus A71 infection.Emerging microbes & infections · 2024Article
- Three modes of viral adaption by the heart.Science advances · 2024Article
113 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1-7. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1-7 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.
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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.