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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng pan Kuiyang Zheng Luc J.Wvan der Laan qiuwei pan Wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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Hepatitis D:advances and challenges

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Chinese Medical Journal 2022年第7期135卷 767-773页

作者： Zhijiang Miao Zhenrong Xie Li Ren qiuwei pan Postgraduate School Molecular Medicine Erasmus MC-University Medical CenterRotterdamThe Netherlands Biobank The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China Department of Obstetrics and Gynecology The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650031China Biomedical Research Center Northwest Minzu UniversityLanzhouGansu 730030China

Hepatitis D virus(HDV)infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis,hepatic decompensation,and hepatocellular *** discovered>40 years ago,little attention has been paid to this pathogen from both scientific and public ***,effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from *** this review,we emphasized the recent advances in HDV virology,epidemiology,clinical feature,treatment,and *** not only highlighted the remaining challenges but also the opportunities that can move the field forward.

关键词： Hepatitis D virus Hepatitis B virus Virology Epidemiology Clinical impact Treatment Prevention

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A novel strategy for cancer gene therapy:RNAi

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Chinese Science Bulletin 2006年第10期51卷 1145-1151页

作者： pan qiuwei CAI Rong LIU Xinyuan QIANCheng Xin Yuan Institute of Medicine and Biotechnology Life Science College Zhejiang Sci-Tech University Hangzhou 310018 China Institute of Biochemistry and Cell Biology Shanghai Institutes forBiological Sciences Chinese Academy of Sciences Shanghai 200031China Division of Gene Therapy and Hepatology CIMA University of Navarra Pamplona 31008 Spain

RNA 干扰(RNA ) 由两倍搁浅的 RNA 在 posttranscriptionmediated 的水平导致基因 silencing。为小 double-strandedinterference RNA (siRNA ) 的交货有众多的方法到目标房间，包括非病毒、病毒的向量。在这些方法之中，病毒的向量是... 详细信息

RNA 干扰(RNA ) 由两倍搁浅的 RNA 在 posttranscriptionmediated 的水平导致基因 silencing。为小 double-strandedinterference RNA (siRNA ) 的交货有众多的方法到目标房间，包括非病毒、病毒的向量。在这些方法之中，病毒的向量是更有效的车辆。由在目标房间的病毒的向量的短发卡 RNA (shRNA ) 的表示能被 Dicer 酶切成为约 21 bp siRNA，它能指导血缘的 mRNA 的降级。RNAi 技术能用许多策略对癌症被指导，包括抑制，支持 apoptosis，调整房间周期在上表示了 oncogenes， antiangiogenesis 并且提高化疗和放射疗法的功效。因为 RNAi 技术为癌症基因治疗成为了优秀策略，这评论构画出如此的一种新奇技术的最近的开发和应用程序。

关键词： RNAi RNA干涉肿瘤基因疗法

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Significance of continuous rotavirus and norovirus surveillance in Indonesia

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World Journal of Pediatrics 2018年第1期14卷 4-12页

作者： Mohamad Saifudin Hakim Hera Nirwati Abu Tholib Aman Yati Soenarto qiuwei pan Department of Gastroenterology and Hepatology ErasmusMC-University Medical Center and Postgraduate SchoolMolecular MedicineRoom Na-1001's-Gravendijkwal2303015CE RotterdamThe Netherlands Department of Micr obiology Faculty of MedicineUniversitas Gadjah MadaYogyakartaIndonesia Department of Child Health Faculty of MedicineUniversitas Gadjah MadaYogyakartaIndonesia

Background Diarrhea significantly contributes to the global burden of diseases, particularly in developing countries. Rota-virus and norovirus are the most dominant viral agents responsible for diarrheal disease globally. The aim of this review was to conduct a comprehensive assessment of rotavirus and norovirus study in Indonesia. Data sources Articles about rotavirus and norovirus surveillance in Indonesia were collected from databases, including PubMed and Google Scholar. Manual searching was performed to identify additional studies. Furthermore, relevant articles about norovirus diseases were included. Results A national surveillance of rotavirus-associated gastroenteritis has been conducted for years, resulting in substantial evidence about the high burden of the diseases in Indonesia. In contrast, norovirus infection received relatively lower attention and very limited data are available about the incidence and circulating genotypes. Norovirus causes sporadic and epidemic gastroenteritis globally. It is also emerging as a health problem in immunocompromised individuals. During post-rotavirus vaccination era, norovirus potentially emerges as the most frequent cause of diarrheal diseases. Conclusions Our review identifies knowledge gaps in Indonesia about the burden of norovirus diseases and the circulating genotypes. Therefore, there is a pressing need to conduct national surveillance to raise awareness of the community and national health authority about the actual burden of norovirus disease in Indonesia. Continuing rotavirus surveillance is also important to assess vaccine effectiveness and to continue tracking any substantial changes of circulating rotavirus genotypes.

关键词： Diarrhea Rotavirus Norovirus Indonesia Surveillance

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Hepatitis E virus infection induces mitochondrial fusion to facilitate viral replication

Hepatitis E virus infection induces mitochondrial fusion to ...

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第十五届中国体视学与图像分析学术会议

作者： Yijin Wang qiuwei pan Jingmin Zhao Department of Pathology and Hepatology Beijing 302 Hospital Department of Gastroenterology and Hepatology Erasmus MC-University Medical Center

Competing Interests:The authors have declared that no competing interests ***:The liver contains abundant copies of mitochondria,which play important roles in physiology and *** have been reported to disrupt mitochondrial machinery by manipulating their dynamics including the processes of fusion and fission to facilitate viral *** study

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大气多参数激光雷达在化工园区的安全环保和碳监测中的应用

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红外与激光工程 2024年第5期53卷 151-163页

作者：夏秋炜章振余赛芬夏海云潘凡峰南京信息工程大学大气物理学院江苏南京210044 国家碳计量中心(福建) 福建南平353011 福建瑞碳光电精密仪器有限公司福建南平353011

化工产业是国家经济发展的基础,但其在促进经济发展的同时也面临着高碳排放、环境污染和安全风险等挑战。为了保障化工园区的平稳运行,团队研制了一套全光纤体制的1.5μm大气多参数激光雷达系统,并应用于化工园区的污染强度、气体浓度... 详细信息

化工产业是国家经济发展的基础,但其在促进经济发展的同时也面临着高碳排放、环境污染和安全风险等挑战。为了保障化工园区的平稳运行,团队研制了一套全光纤体制的1.5μm大气多参数激光雷达系统,并应用于化工园区的污染强度、气体浓度、风场和降雨信息的监测和预警。该激光雷达系统集成了直接探测模块和相干探测模块,在直接探测模块中,基于扫描光源和超导纳米线单光子探测器进行气体浓度的监测。在相干探测模块中,基于对距离修正回波信号、载噪比和多普勒频移的分析获得颗粒物污染强度和风场分布;基于湍流动能耗散率和风廓线的速度梯度获得湍流和风切变信息;基于深度功率谱分析获得谱宽和偏度,用于区分风速和雨速,获得精准的降雨信息。大气多参数激光雷达分别在江苏省南京市江北新区和内蒙古自治区鄂尔多斯自治旗棋盘井镇进行外场实验,通过多次实验验证了该大气多参数激光雷达在化工园区进行环保、安全和精细化气象保障的能力。文中还进一步设计展望了该系统在化工园区探测多种危化气体浓度的潜力。

关键词：激光雷达化工园区环境监测大气遥感

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Chronic hepatitis E in a renal transplant recipient:the first report of genotype 4 HEV caused chronic infection in organ recipient

Chronic hepatitis E in a renal transplant recipient:the firs...

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第十五届中国体视学与图像分析学术会议

作者： Yijin Wang Yunlong Li Dong Ji Fen Huang qiuwei pan Guofeng Chen Jingmin Zhao Department of Pathology and Hepatology Beijing 302 Hospital Medical Faculty Kunming University of Science and Technology Department of Gastroenterology and Hepatology Erasmus MC-University Medical Center Second Liver Cirrhosis Diagnosis and Treatment Center 302 Hospital

Background:Hepatitis E virus(HEV) normally causes acute infection but also chronic hepatitis in immunocompromised population,especially in organ transplant recipients receiving immunosuppressants for preventing organ ***,only genotype 3 HEV has been attributed to chronic infection in transplant ***,we report the first case of genotype 4 HEV caused chronic infection in a renal transplant recipient with long-term immunosuppressive *** have profiled the pathological and serological features of this ***:HEV persistent infection was determined by serological examination of anti-HEV IgM *** electron microscope(TEM) was performed to observe HEV viral particles and hepatocellular ultrastructure in liver *** was performed to detect HEV viral protein and fibrotic status in liver *** genotype of the patient was determined by nested-polymerase chain reaction(PCR) and sequencing of stool ***:This patient received kidney transplant 9 years ago and has been detected with HEV infection for 4 years according to the immunologic test of persistent positive anti-HEV *** therapy was used to treat this patient and resulted in liver function normalization,but was intervened due to anaemia and renal *** serological examination showed positive anti-HEV IgM(6.78) and negative indicators for HAV,HBV,HCV and ***-PCR and sequencing of the patient’ stool indicated a genotype 4 HEV *** of liver biopsy with anti-HEV antibody further confirmed the infection and expression of viral ***,the HEV viral particles were visualized in liver tissue by ***,hepatocellular ultrastructure by TEM imaging showed injured mitochondria which displayed swollen shape and obscure cristae of hepatocytes,as well as unusually abundant of autophagosomes,indicating the occurrence of liver ***,reticulum fiber staining revealed the develop

关键词： Chronic hepatitis E Genotype 4 organ transplantation

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转录因子p53与脑出血铁死亡的研究进展

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中国医药 2024年第3期19卷 469-471页

作者：李知阳雷盼华秋伟蔡强武汉大学人民医院神经外科武汉430060

脑出血是死亡率最高的脑卒中亚型,占脑血管疾病的35%,具有高致残、致死率。铁死亡是一种铁依赖性非凋亡细胞死亡模式,近年来发现在脑卒中存在铁死亡现象。p53作为一种转录因子,p53表达不足的情况下可以促进铁死亡的发生;此外,通过各种... 详细信息

脑出血是死亡率最高的脑卒中亚型,占脑血管疾病的35%,具有高致残、致死率。铁死亡是一种铁依赖性非凋亡细胞死亡模式,近年来发现在脑卒中存在铁死亡现象。p53作为一种转录因子,p53表达不足的情况下可以促进铁死亡的发生;此外,通过各种代谢途径p53能够在存在铁死亡诱导剂(如谷胱甘肽过氧化酶4抑制剂或高水平的活性氧)的情况下抑制铁死亡。p53作为典型和非典型铁死亡途径的关键调节因子参与铁死亡的调节。本文就p53与脑出血后铁死亡脑损伤关系的研究进展进行综述。

关键词：脑出血转录因子p53 铁死亡继发性脑损伤

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Combined antiviral activity of interferon-α and RNA interference directed against hepatitis C without affecting vector delivery and gene silencing

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世界最新医学信息文摘 2017年第30期 281-281页

作者： qiuwei pan Scot D.Henry Herold J.Metselaar Bob Scholte Jaap Kwekkeboom Hugo W.Tilanus Harry L.A.Janssen Luc J.W.van der Laan

The current standard interferon-alpha(IFN-α)-based therapy for chronic hepatitis C virus(HCV) infection is only effective in approximately half of the patients,prompting the need for alternative *** interference(RNAi)represents novel approach to combat HCV by sequence-specific targeting of viral or host factors involved in *** of RNAi,however,may lead to therapeutic resistance by mutational escape of the ***,we proposed that combining lentiviral vector-mediated RNAi and IFN-a could be more effective and avoid therapeutic *** this study,we found that IFN-α treatment did not interfere with RNAi-mediated gene *** and IFN-α act independently on HCV replication showing combined antiviral activity when used simultaneously or *** ofmouse hepatocytes in vivo and in vitro was not effected by IFN-α *** conclusion,RNAi and IFN-a can be effectively combined without crossinterference and may represent a promising combinational strategy for the treatment of hepatitis C.

关键词： RNAi IFN-α Gene therapy Lentiviral vector HCV

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Combined antiviral activity of interferon-α and RNA interference directed against hepatitis C without affecting vector delivery and gene silencing

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世界最新医学信息文摘 2016年第11期 8-8页

作者： qiuwei pan Scot D.Henry Herold J.Metselaar Bob Scholte Jaap Kwekkeboom Hugo W.Tilanus Harry L.A.Janssen Auc J.W.van der Laan

The current standard interferon-alpha(IFN-α)-based therapy for chronic hepatitis C virus(HCV) infection is only effective in approximately half of the patients, prompting the need for alternative treatments. RNA interference(RNAi) represents novel approach to combat HCV by sequence-specific targeting of viral or host factors involved in infection. Monotherapy of RNAi, however, may lead to therapeutic resistance by mutational escape of the virus. Here, we proposed that combining lentiviral vector-mediated RNAi and IFN-α could be more effective and avoid therapeutic resistance. In this study, we found that IFN-α treatment did not interfere with RNAi-mediated gene silencing. RNAi and IFN-α act independently on HCV replication showing combined antiviral activity when used simultaneously or sequentially. Transduction ofmouse hepatocytes in vivo and in vitro was not effected by IFN-α treatment. In conclusion, RNAi and IFN-α can be effectively combined without crossinterference and may represent a promising combinational strategy for the treatment of hepatitis c.

关键词： RNAi IFN-α Gene therapy Lentiviral vector HCV

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