Coptisine Inhibits Influenza Virus Replication by Upregulating p21
Ming-Feng He,
Jian-Hui Liang,
Yan-Ni Shen,
Chao-Wei Zhang,
Kuang-Yang Yang,
Li-Chu Liu,
Qian Xie,
Chun Hu,
Xun Song,
Yan Wang
Affiliations
Ming-Feng He
Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China
Jian-Hui Liang
Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Yan-Ni Shen
Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Chao-Wei Zhang
School of Pharmaceutical Science, Shenzhen University, Shenzhen 518000, China
Kuang-Yang Yang
Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China
Li-Chu Liu
Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China
Qian Xie
Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Chun Hu
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
Xun Song
College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China
Yan Wang
Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
The activation of innate antiviral immunity is a promising approach for combatting viral infections. In this study, we screened Chinese herbs that activated human immunity and identified coptisine as a potent inhibitor of the influenza virus with an EC50 of 10.7 μM in MDCK cells. The time of an addition assay revealed that pre-treatment with coptisine was more effective at reducing viral replication than co-treatment or post-treatment. Our bulk RNA-sequencing data showed that coptisine upregulated the p21 signaling pathway in MDCK cells, which was responsible for its antiviral effects. Specifically, coptisine increased the expression of p21 and FOXO1 in a dose-dependent manner while leaving the MELK expression unchanged. Docking analysis revealed that coptisine likely inhibited MELK activity directly by forming hydrogen bonds with ASP-150 and GLU-87 in the catalytic pocket. These findings suggest that coptisine may be a promising antiviral agent that regulates the p21 signaling pathway to inhibit viral replication.
