Authors
Meng Chen, Nannan Zhang, Qifei Wu, Yin Cao, Zihan Zhang, Xiuqi Tang, Borui Zhao, Cancan Zhu, Yingying Li, Xudong Qiu, Ziyuan Chu, Kexuan Bao, Xiaohui Xu, Lei Hu
Published in
European journal of pharmacology. Pages 179530. Nov 10, 2026. Epub Nov 10, 2026.
Abstract
The continuous emergence of SARS-CoV-2 variants (e.g., JN.1, KP.3) and the significantly elevated risk of severe COVID-19 in patients with rheumatic autoimmune diseases highlight an urgent unmet clinical need for dual-targeted therapeutics. Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound with a long history of clinical use in China, prevents SARS-CoV-2 infection by downregulating the viral entry receptor ACE2 through inhibition of HIF-1α and JAK2/STAT3 signaling. This review synthesizes the pleiotropic pharmacological mechanisms of daphnetin, including anti-inflammatory (NF-κB, JAK/STAT, NLRP3), antioxidant (Nrf2/Keap1), immunomodulatory (Th17/Treg balance), and mitochondrial protective pathways. These pathways are critically involved in the pathogenesis of both severe COVID-19 and rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We propose that daphnetin represents a novel "one agent, dual protection" strategy: it not only blocks viral entry by reducing ACE2 but also mitigates the hyperinflammatory and oxidative stress states that exacerbate both COVID-19 severity and rheumatic disease activity. Given its established safety, oral activity, and low cost, daphnetin is a promising candidate for clinical translation in high-risk comorbid populations. Key unresolved questions and future research directions are also discussed.
PMID:
43009037
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.
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