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A nitrogen-containing diphyllin derivative C156-P1 exhibited broad-spectrum antiviral activity against Flaviviridae viruses by preventing endosomal acidification

文献类型：期刊论文

作者Chen, Guoquan7,8; Li, Wanfei4,5,6; Lam, Ka Hei6; Hu, Mingyue7; Wu, Qian7; Xu, Xiangyu7; Huang, Yunzhu7; Tang, Fei7; Cui, Guohui7; Cui, Ping3
刊名ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
出版日期2025-09-26
页码23
关键词plant natural products nitrogen-containing diphyllin derivatives Flaviviridae viruses dengue virus
ISSN号0066-4804
DOI10.1128/aac.00527-25
英文摘要Dengue virus (DENV) represents a significant public health threat, with its four serotypes estimated to account for approximately 96 million symptomatic infections annually. Currently, there are no antiviral agents available for the prevention or treatment of DENV infection. Here, we initially screened 12 diphyllin derivatives and identified C156-P1, a nitrogen-containing compound, as a potent agent against DENV infection. Further, C156-P1 exhibited inhibitory effects against the viruses of the Flaviviridae family, including four serotypes of DENV (DENV-1 to DENV-4) in multiple human and monkey cell lines, as well as Zika virus, Japanese encephalitis virus, yellow fever virus, and hepatitis C virus. In addition, C156-P1 also showed inhibition of the infections of herpes simplex virus type 1 and vesicular stomatitis virus, but not adenovirus and Sendai virus. Mechanistic studies demonstrated that C156-P1 inhibited DENV-2 after cell entry but before the endosomal membrane fusion step. C156-P1 inhibited vacuolar-type ATPase activity by perturbing the expression of ATP6V0A2 subunit, thereby suppressing endosomal acidification. Consequently, DENV was restricted in the late endosome, inhibiting virus fusion with endosomal membranes and resulting in infection inhibition. C156-P1 treatment also suppressed both IFN-I responses and endosomal TLR3 activation induced by DENV-2 infection. Furthermore, administration of C156-P1 in AG129 mice significantly reduced DENV-2 infection and effectively increased the survival rate of the mice. Taken together, our study demonstrates that the novel nitrogen-containing diphyllin derivative C156-P1 functions as a broad-spectrum antiviral agent by inhibiting endosomal acidification, thus representing a promising host-targeting antiviral candidate for future development.
WOS关键词VESICULAR STOMATITIS-VIRUS ; HEPATITIS-C VIRUS ; DENGUE VIRUS ; V-ATPASE ; HOST-CELLS ; INHIBITOR ; ENTRY ; DRUG ; RECOGNITION ; MECHANISMS
资助项目The Science and Technology Planning Project of Guangdong Province, China
WOS研究方向Microbiology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001579731000001
出版者AMER SOC MICROBIOLOGY
源URL[http://119.78.100.183/handle/2S10ELR8/321582]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Qian, Jun; Zhang, Hong-Jie; Li, Yi-Ping
作者单位1.Guangzhou Med Univ, Guangzhou Peoples Hosp 8, Inst Infect Dis, Guangzhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai, Peoples R China
3.Guangxi Med Univ, Life Sci Inst, Nanning, Peoples R China
4.Guangzhou Pharmaceut Holdings Ltd, Postdoctoral Res Ctr, Guangzhou, Peoples R China
5.Jinan Univ, Affiliated Hosp 1, Guangzhou, Peoples R China
6.Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China
7.Sun Yat Sen Univ, Inst Human Virol, Zhongshan Sch Med,Dept Pathogen Biol & Biosecur, Key Lab Trop Dis Control,Minist Educ, Guangzhou, Peoples R China
8.Guangxi Univ, Coll Anim Sci & Technol, Nanning, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Guoquan,Li, Wanfei,Lam, Ka Hei,et al. A nitrogen-containing diphyllin derivative C156-P1 exhibited broad-spectrum antiviral activity against Flaviviridae viruses by preventing endosomal acidification[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2025:23.
APA Chen, Guoquan.,Li, Wanfei.,Lam, Ka Hei.,Hu, Mingyue.,Wu, Qian.,...&Li, Yi-Ping.(2025).A nitrogen-containing diphyllin derivative C156-P1 exhibited broad-spectrum antiviral activity against Flaviviridae viruses by preventing endosomal acidification.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,23.
MLA Chen, Guoquan,et al."A nitrogen-containing diphyllin derivative C156-P1 exhibited broad-spectrum antiviral activity against Flaviviridae viruses by preventing endosomal acidification".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2025):23.

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来源：上海药物研究所

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