Citation: Yang Li, Ning Sheng, Kun Wang, Yuhuan Li, Jiandong Jiang, Jinlan Zhang. Azvudine alleviates SARS-CoV-2-induced inflammation by targeting myeloperoxidase in NETosis[J]. Chinese Chemical Letters, ;2025, 36(5): 110238. doi: 10.1016/j.cclet.2024.110238 shu

Azvudine alleviates SARS-CoV-2-induced inflammation by targeting myeloperoxidase in NETosis

Yang Li ^{a, 1} ,
Ning Sheng ^{a, 1} ,
Kun Wang ^b ,
Yuhuan Li ^b ,
Jiandong Jiang ^{a, b, *,} ,
Jinlan Zhang ^{a, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
b.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China

jiang.jdong@163.com

zhjl@imm.ac.cn

Received Date: 1 April 2024
Revised Date: 16 June 2024
Accepted Date: 10 July 2024
Available Online: 11 July 2024

Figures(6)

Neutrophil extracellular traps (NETs) formation (NETosis), is a crucial immune system mechanism mediated by neutrophils, measuring the capacity to induce NETosis is proposed as a clinical biomarker indicating the severity of COVID-19 and long COVID. Azvudine (FNC), has shown efficacy in treating SARS-CoV-2 infection and potential for alleviating inflammation. However, the molecular mechanism underlying its anti-inflammatory effects has not been extensively investigated. Therefore, a series of experiments were conducted on SARS-CoV-2 infected rhesus macaques (RMs) to investigate the anti-inflammatory effects of FNC. The experiments involved HE staining, mass spectrometry-based proteomics, validation experiments conducted in vivo using RMs tissues and in vitro differentiation of HL-60 cells. Additionally, interaction investigations were carried out utilizing LiP-MS, CETSA, Co-IP along with molecular docking. The results demonstrated that FNC treatment effectively alleviated neutrophil infiltration and attenuated inflammatory injury following infection. In addition to exhibiting antiviral effects, FNC treatment exhibited a reduction in inflammation-associated proteins and pathways such as myeloperoxidase (MPO) and the formation of NETs, respectively. Validation experiments confirmed the impact of FNC on regulating NETs formation, interaction experiments suggested that MPO may serves as a therapeutic target. The multifaceted properties of FNC, including its antiviral and anti-inflammatory characteristics, highlight the therapeutic potential in diseases associated with NETosis, particularly those involving concurrent SARS-CoV-2 infection, providing insights for drug development targeting MPO and NETosis-associated diseases.
- SARS-CoV-2,
- Azvudine,
- Inflammation,
- NETosis,
- Rhesus macaque,
- Myeloperoxidase
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