A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ASCENDING DOSE STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF JTK-652 ADMINISTERED FOR FOUR WEEKS IN SUBJECTS WITH CHRONIC HEPATITIS C INFECTION - JTK-652 proof of concept study

开始日期2008-01-20

申办/合作机构

Japan Tobacco, Inc.

NL-OMON31189 / CompletedN/A

A phase 1, randomized, double-blind, placebo-controlled, ascending dose study evaluating the safety, tolerability and pharmacokinetics of JTK-652 administered for two weeks in healthy male subjects - JTK-652 multiple ascending dose study

开始日期2007-10-15

申办/合作机构

Japan Tobacco, Inc.

100 项与 HCV E2 相关的临床结果

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100 项与 HCV E2 相关的转化医学

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0 项与 HCV E2 相关的专利（医药）

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179

项与 HCV E2 相关的文献（医药）

2023-10-18·Frontiers in bioscience (Landmark edition)

A Conserved Domain of HCV E2 Glycoprotein Interacts with Human CD81 and Induces Interferon-Gamma Secretion from Peripheral Blood Mononuclear Cells.

Article

作者: Shu, Xin ; Li, Gang ; Zeng, Wei ; Dai, Zhiyan

BACKGROUNDHepatitis C virus (HCV) infection is a global health threat to the public, and vaccines against it are not yet available. The HCV envelope glycoprotein E2 is a key target for anti-HCV vaccines. The majority of previous studies have focused on the hypervariable region and the glycosylation sites of the_HCV structural protein. This study aims to investigate a conserved domain of HCV E2 glycoprotein and explore its potential to induce an immune response against HCV.METHODSHCV E2 conserved domain (encompassing amino acids 505-702) was prepared in Escherichia coli (E. coli). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HCV or healthy controls. Interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot assay was conducted to examine the HCV E2-specific immune response as reflected by IFN-γ-secreting cells/106 PBMCs.RESULTSHCV E2 conserved domain was highly conserved among 25 HCV subtypes, and its recombinant soluble production in E. coli was recognized by anti-HCV E2 monoclonal antibodies. This study characterized in vitro direct interaction between bacterially expressed HCV E2 conserved domain and human CD81 (hCD81). Furthermore, the recombinant HCV E2_conserved domain markedly induced the production of IFN-γ by PBMCs from patients with HCV. Its stimulated specific immune response was significantly different from non-specific peptide controls or PBMCs isolated from healthy controls.CONCLUSIONSHCV E2 conserved domain directly binds hCD81 and activates the production of IFN-γ in the PBMCs of patients with HCV. Therefore, the conserved domain of HCV E2 glycoprotein may be a new candidate for developing an HCV vaccine.

2023-04-13·Microbiology Spectrum

Effect of Glycan Shift on Antibodies against Hepatitis C Virus E2 412–425 Epitope Elicited by Chimeric sHBsAg-Based Virus-Like Particles

Article

作者: Patel, Arvind H. ; Gottwein, Judith Margarete ; Bukh, Jens ; Owsianka, Ania ; Grzyb, Katarzyna ; Alzua, Garazi Peña ; Offersgaard, Anna ; Bieńkowska-Szewczyk, Krystyna ; Czarnota, Anna

Epitope I, located within amino acids 412 to 423 of the HCV E2 glycoprotein, is an important target for an epitope-based HCV vaccine. One interesting feature of epitope I is the N417 glycosylation site, where a single change to S417 or T417 can shift the glycosylation site to position N415.

2023-04-06·Cancers

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases.

Review

作者: Bailly, Christian ; Thuru, Xavier

Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.