ArticleCellular and molecular life sciences : CMLS2022
The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of zapnometinib: results from a phase I clinical study.Frontiers in pharmacology · 2026Trial
- Antiviral and immunomodulatory effect of zapnometinib in animal models and hospitalized COVID-19 patients.Frontiers in immunology · 2025Trial
- Dual host and pathogen targeting by MEK1/2 inhibitors.Infection and immunity · 2026Review
- MEK Inhibitors and Toll-like Receptor Signaling: Implications for Infection and Inflammation.International journal of molecular sciences · 2026Review
- Review
- MEK1/2 inhibitor ATR-002 reshapes host transcriptome and modulates immune regulatory genes in SARS-CoV-2 infection.Frontiers in immunology · 2026Article
- Zapnometinib treatment and influenza A virus infection modulate the HLA class I ligandome in human lung adenocarcinoma cells.Frontiers in immunology · 2026Article
- Benzydamine Attenuates Matrix Metalloproteinase-9 Expression Through Inhibition of ERK MAPK in Activated Human Monocytic Cells Under Hyperglycemic Condition.Mediators of inflammation · 2026Article
- Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib.Emerging microbes & infections · 2025Article
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- Article
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- Suppressive effect of isofraxidin on the overexpression of IL-6 and its molecular mechanism in a TPA-treated human hepatocellular carcinoma cell line, HuH-7.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Analysis of phosphomotifs coupled to phosphoproteome and interactome unveils potential human kinase substrate proteins in SARS-CoV-2.Frontiers in cellular and infection microbiology · 2025Article
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20-24, 2024, organized by the International Society for Antiviral Research.Antiviral research · 2024Article
- Inhibition of RAN attenuates influenza a virus replication and nucleoprotein nuclear export.Emerging microbes & infections · 2024Article
- EGFR-MEK1/2 cascade negatively regulates bactericidal function of bone marrow macrophages in mice with Staphylococcus aureus osteomyelitis.PLoS pathogens · 2024Article
- Hexestrol, an estrogen receptor agonist, inhibits Lassa virus entry.Journal of virology · 2024Article
- Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections.International journal of molecular sciences · 2024Review
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15 authors at 6 institutions in 1 country.
Funding
Abstract
Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 million deaths to date. While vaccination is a powerful tool to control pandemic spread, medication to relieve COVID-19-associated symptoms and alleviate disease progression especially in high-risk patients is still lacking. In this study, we explore the suitability of the rapid accelerated fibrosarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway as a druggable target in the treatment of SARS-CoV-2 infections. We find that SARS-CoV-2 transiently activates Raf/MEK/ERK signaling in the very early infection phase and that ERK1/2 knockdown limits virus replication in cell culture models. We demonstrate that ATR-002, a specific inhibitor of the upstream MEK1/2 kinases which is currently evaluated in clinical trials as an anti-influenza drug, displays strong anti-SARS-CoV-2 activity in cell lines as well as in primary air-liquid-interphase epithelial cell (ALI) cultures, with a safe and selective treatment window. We also observe that ATR-002 treatment impairs the SARS-CoV-2-induced expression of pro-inflammatory cytokines, and thus might prevent COVID-19-associated hyperinflammation, a key player in COVID-19 progression. Thus, our data suggest that the Raf/MEK/ERK signaling cascade may represent a target for therapeutic intervention strategies against SARS-CoV-2 infections and that ATR-002 is a promising candidate for further drug evaluation.
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Registered trials
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