Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters

作     者：Xinna Ma Heng Li Ying Gong Feifei Liu Xiankun Tong Fenghua Zhu Xiaoqian Yang Li Yang Jianping Zuo Xinna Ma;Heng Li;Ying Gong;Feifei Liu;Xiankun Tong;Fenghua Zhu;Xiaoqian Yang;Li Yang;Jianping Zuo

作者机构：Laboratory of Immunology and VirologyShanghai University of Traditional Chinese MedicineShanghai201203China Laboratory of ImmunopharmacologyState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of SciencesBeijing100049China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2022年第37卷第2期

页      面：256-265页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by the National Science Fund (82104240) Shanghai Science and Technology Innovation Project (20S11906200) self-deployed scientific research projects (State Key Laboratory of Drug Research) (SIMM1903ZZ-03) 

主　　题：Psoralen Hepatitis B virus(HBV) Forkhead box-O1(FOXO1) PPARγco-activator 1α(PGC1α) Transcription 

摘      要：The hepatitis B virus(HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV *** PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in Hep G2.2.15 cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV precore/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1αto the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by downregulating the expression of FOXO1 resulting in a reduction of HBV replication.