期刊
BIOORGANIC CHEMISTRY
卷 129, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.106118
关键词
Triptolide derivatives; Antiviral; Influenza A virus; Nucleoprotein; Inflammation
资金
- National Natural Science Foundation of China [81860618, 22067012]
- Innovative Team of Yunnan Province [2019HC018]
- Higher Educational Key Laboratory for New drugs for Viral Respiratory Diseases (Chinese Traditional Medicine) of Yunnan Province
- Key Project of Research and Development of Yunnan Province [202103AC10005]
This study found that TP derivatives have antiviral activity and anti-inflammatory effects against influenza A virus by inhibiting viral replication and regulating immune response. They could be potential candidates for antiviral drugs.
Triptolide (TP) is a major active compound derived from the traditional Chinese medicine Tripterygium wilfordii. TP has been reported to inhibit the infection of HIV and a few other viruses. However, the antiviral spectrum and the underlying mechanisms of TP are incompletely defined. TP derivatives were designed, synthesized, and evaluated for anti-influenza activity against the influenza A virus in this study. All of them exhibited activities against oseltamivir sensitive influenza A/WSN/33 virus (H1N1) and oseltamivir resistant influenza A/PR/8/33 virus (H1N1) with low cytotoxicity in vitro. In our present study, TP derivatives probably suppressed influenza virus replication through inhibiting ribonucleoprotein complex nucleus export of influenza A virus by binding with viral nucleoprotein. Moreover, TP derivatives downregulated influenza A virus-induced macrophage cytokine storm in a dose-dependent manner, through inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappa B) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling. Taken together, TP derivatives suppressed influenza A virus replication by directly targeting NP and regulating innate immune responses induced by influenza A virus infection, which suggested that TP derivatives might be prospective candidates for potent antivirals.
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