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Acta Pharmaceutica Sinica B 2018年第2期8卷 200-208页

作者： Qing Chen Ke Tang Xiaoyu Zhang Panpan Chen Ying Guo State Key Laboratory of Bioactive Substances and Function of Natural Medicines Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College

Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4(BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and *** HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here,we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.

关键词： Filovirus Ebola Marburg Pseudovirus entry inhibitor Mouse model

Closing the door to human immunodeficiency virus

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Protein & Cell 2013年第2期4卷 86-102页

作者： Yuanxi Kang Jia Guo Zhiwei Chen AIDS Institute and Department of Microbiology of Li Ka Shing Faculty of Medicine The University of Hong Kong21 Sassoon RoadPokfulamHong Kong SARChina Research Center for Infection and Immunity The University of Hong Kong21 Sassoon RoadPokfulamHong Kong SARChina

The pandemic of human immunodeficiency virus type one(HIV-1),the major etiologic agent of acquired immunodeficiency disease(AIDS),has led to over 33 million people living with the virus,among which 18 million are women and *** now,there is neither an effective vaccine nor a therapeutic cure despite over 30 years of *** the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%,an effective vaccine will likely rely on a break-through discovery of immunogens to elicit broadly reactive neutralizing antibodies,which may take years to ***,there is an urgency of exploring other prophylactic ***,antiretroviral treatment as prevention is an exciting area of pro-gress in HIV-1 *** effective,the im-plementation of such strategy faces great financial,political and social challenges in heavily affected re-gions such as developing countries where drug re-sistant viruses have already been found with growing *** latently infected cells for thera-peutic cure is another area of *** it is greatly difficult to eradicate HIV-1 after the establish-ment of viral latency,it is necessary to investigate strategies that may close the door to ***,we review studies on non-vaccine strategies in targeting viral entry,which may have critical implications for HIV-1 prevention.

关键词： HIV-1 entry inhibitor vaccine antiretrovi-ral antibody

Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4378-4389页

作者： Dongrong Yi Quanjie Li Han Wang Kai Lv Ling Ma Yujia Wang Jing Wang Yongxin Zhang Mingliang Liu Xiaoyu Li Jianxun Qi Yi Shi George F.Gao Shan Cen Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical SchoolBeijing 100050China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAMS Key Laboratory of Antiviral Drug Research Institute of Medicinal BiotechnologyPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100050China

Ebola virus(EBOV)infection leads to staggeringly high mortality *** and low-cost treatments are urgently needed to control frequent EBOV outbreaks in *** this study,we report that a natural compound called berbamine hydrochloride strongly inhibits EBOV replication in vitro and in *** work further showed that berbamine hydrochloride acts by directly binding to the cleaved EBOV glycoprotein(GPcl),disrupting GPcl interaction with viral receptor Niemann-Pick C1,thus blocking the fusion of viral and cellular *** data support the probability of developing anti-EBOV small molecule drugs by targeting viral *** importantly,since berbamine hydrochloride has been used in clinic to treat leukopenia,it holds great promise of being quickly repurposed as an anti-EBOV drug.

关键词： Ebola virus Drug repositioning entry inhibitor Primed glycoprotein Structure-based virtual screening Protein-protein interaction Berbamine hydrochloride Natural compound

Virus-host Interactions during Hepatitis C Virus entry-Implications for Pathogenesis and Novel Treatment Approaches

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Virologica Sinica 2008年第2期23卷 124-131页

作者： Joachim Lupberger Mirjam B. Zeisel Anita Haberstroh Eva K. Schnober Sophie Krieger Eric Soulier Christine Thumann Cathy Royer Samira Fafi-Kremer Catherine Schuster Franoise Stoll-Keller Hubert E. Blum Thomas F. Baumert Inserm U748 Hpitaux Universitaires de Strasbourg Université Louis Pasteur 3 Rue Koeberle Department of Medicine II University of Freiburg

Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.

关键词： Hepatitis C virus Viral entry entry inhibitor Neutralizing antibodies