期刊
ANTIVIRAL RESEARCH
卷 193, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2021.105143
关键词
Cepharanthine; HSV-1; Autophagy; Antiviral; STING/TBK1/P62 pathway
资金
- National Natural Science Foundation of China [82074094]
- Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of System-atic Research of Distinctive Chinese Medicine Resources in Southwest China [2020XSGG002]
- Xinglin Scholar Research Promo-tion Project of Chengdu University of Traditional Chinese Medicine [CDTD2018014]
- Applied Basic Research Project of Sci-ence and Technology Department of Sichuan Province [20YYJC0640]
- Key project of the education department of Sichuan Province [18ZB0152, 18ZA0162]
Cepharanthine (CEP), a naturally occurring compound extracted from plants, shows inhibitory effects against HSV-1 infection by promoting autophagy to degrade viral particles and cellular components.
Cepharanthine (CEP), a naturally occurring isoquinoline alkaloid extracted from the genus CEP of the Tetrandrine family, was reported to possess many biological activities such as anti-inflammatory, antitumor, antiviral, and immune-enhancing effects. Nevertheless, the underlying mechanisms of CEP against herpes simplex virus type 1 (HSV-1) are still elusive. In this study, we explored the anti-HSV effects and mechanisms of CEP in vitro. The results showed that CEP possessed a strong inhibitory effect against HSV-1 infection with the TC50 of 5.4 mu g/mL, the IC50 of 0.835 mu g/mL, and the TI of 6.47. Most importantly, CEP could promote the phosphorylation of STING, TBK1, and P62 and the expression of LC3II without induction of interferon by directly targeting the STING/TBK1/P62 signaling pathways. Electron microscopy showed that autophagy induced by CEP could degrade viral particles and cellular components. RT-PCR results revealed that a sharp reduction of large numbers of virus gene transcription in 16 h after CEP treatment. Furthermore, CEP also reduced the HSV-1 gB and gC transcription. In conclusion, one of the effects of CEP was to promote interferon-independent autophagy through STING mediated signaling.
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