This study has two parts. Part A will assess the safety, tolerability and pharmacokinetics (PK) of AT-777 in healthy subjects. Part B will assess the safety, antiviral activity/efficacy and PK of AT-777 in combination with AT-527 after 8 weeks of treatment in HCV-infected subjects.

开始日期2021-10-01

申办/合作机构

Atea Pharmaceuticals, Inc.

CTR20202688 / Completed临床1期

TQ-A3326片与百立泽在健康成年受试者中的药代动力学比对试验

本试验目的是参考生物等效性评价方法，研究正大天晴药业集团股份有限公司提供的TQ-A3326片与AstraZenecaPharmaceuticalsLP生产的百立泽TM在健康成年受试者中的生物利用度及药代动力学特点，用以支持TQ-A3326片的注册申报。

开始日期2021-01-25

申办/合作机构

正大天晴药业集团股份有限公司

[+1]

CTR20192091 / Completed临床1期

在健康受试者中评价ASC18片中RDV与SOF的药物相互作用、食物影响及药代动力学研究

评价ASC18片（RDV/SOF复方片）中RDV与SOF的药物相互作用；评价食物对ASC18片药代动力学的影响；比较ASC18片与RDV片和SOF片（RDV+SOF）联用的药动学参数。

开始日期2020-04-12

申办/合作机构

歌礼药业（浙江）有限公司

100 项与 Hepatitis C virus NS 5 protein 相关的临床结果

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100 项与 Hepatitis C virus NS 5 protein 相关的转化医学

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0 项与 Hepatitis C virus NS 5 protein 相关的专利（医药）

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项与 Hepatitis C virus NS 5 protein 相关的文献（医药）

2018-11-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

Molecular Neuroprotection Induced by Zinc-Dependent Expression of Hepatitis C–Derived Protein NS5A Targeting Kv2.1 Potassium Channels

3区 · 医学

Article

作者: Palladino, Michael J ; Justice, Jason A ; Yeh, Chung-Yang ; Hartnett-Scott, Karen A ; Aizenman, Elias ; Manjooran, Daniel T ; Schulien, Anthony J ; Mammen, Shalom ; Kosobucki, Gabrielle J

We present the design of an innovative molecular neuroprotective strategy and provide proof-of-concept for its implementation, relying on the injury-mediated activation of an ectopic gene construct. As oxidative injury leads to the intracellular liberation of zinc, we hypothesize that tapping onto the zinc-activated metal regulatory element (MRE) transcription factor 1 system to drive expression of the Kv2.1-targeted hepatitis C protein NS5A (hepatitis C nonstructural protein 5A) will provide neuroprotection by preventing cell death-enabling cellular potassium loss in rat cortical neurons in vitro. Indeed, using biochemical and morphologic assays, we demonstrate rapid expression of MRE-driven products in neurons. Further, we report that MRE-driven NS5A expression, induced by a slowly evolving excitotoxic stimulus, functionally blocks injurious, enhanced Kv2.1 potassium whole-cell currents and improves neuronal viability. We suggest this form of "on-demand" neuroprotection could provide the basis for a tenable therapeutic strategy to prevent neuronal cell death in neurodegeneration.

2008-06-01·Journal of Viral Hepatitis2区 · 医学

Strategies for loading dendritic cells with hepatitis C NS5a antigen and inducing protective immunity

2区 · 医学

Article

作者: H. Yu ; L. A. Babiuk ; S. Van Drunen Littel‐van den Hurk

Summary. Dendritic cell (DC)‐based vaccination strategies are promising for the treatment of cancers and infectious diseases including hepatitis C virus (HCV). As the induction of T cell‐mediated immune responses by DC vaccination is highly dependent on efficient antigen loading of the DCs, the purpose of this study was to identify an optimal nonviral DC loading strategy for HCV NS5a. Furthermore, the efficacy of immunization with the NS5a‐loaded DCs in comparison to plasmid encoding NS5a and NS5a protein was evaluated. Transfection of DCs with mRNA was most efficient with close to 100% of DCs expressing NS5a, whereas approximately 10% of protein‐pulsed DCs and <1% of plasmid‐transfected DCs expressed NS5a, suggesting remarkably different loading efficiencies. Vaccination of mice with NS5a mRNA‐transfected DCs or NS5a protein‐pulsed DCs resulted in significantly stronger CD4+ and CD8+ T‐cell responses and protection from challenge with vaccinia virus expressing NS3/NS4/NS5, in comparison to vaccination with NS5a DNA‐transfected DCs, plasmid encoding NS5 or rNS5a protein formulated with alum. Furthermore, vaccination with NS5a mRNA‐transfected DCs was superior to vaccination with rNS5a‐pulsed DCs. These data have important clinical implications, with mRNA‐transfected DCs providing a safe and effective vaccination strategy against hepatitis C and possibly other pathogens.

Molekuliarnaia biologiia

[DNA immunization with a plasmid containing gene of hepatitis C virus protein 5A (NS5A) induces the effective cellular immune response].

Article

作者: Lesnova, E I ; Ataullakhanov, R I ; Smirnova, O A ; Grabovetskiĭ, V V ; Zaberezhnyĭ, A D ; Masalova, O V ; Ivanov, A V ; Kushch, A A ; Ulanova, T I ; Burkov, A N

In spite of extensive research, no effective vaccine against hepatitis C virus (HCV) has been developed so far. DNA immunization is a potent technique of vaccine design strongly promoting the cellular arm of immune response. The genes encoding nonstructural HCV proteins (NS2-NS5B) are promising candidates for vaccine development. NS5A is a protein involved in viral pathogenesis, in the induction of immune response, and probably in viral resistance to interferon treatment. The objective of this study was to construct a DNA vaccine encoding NS5A protein and evaluate its immunogenicity. A plasmid encoding a full-size NS5A protein was produced using the pcDNA3.1 (+) vector for eukaryotic expression system. The expression of the NS5A gene was confirmed by immunoperoxidase staining of the transfected eukaryotic cells with anti-NS5A monoclonal antibodies. Triple immunization of mice with the plasmid vaccine induced a pronounced cellular immune response against abroad spectrum of NSSA epitopes as assessed by T-cell proliferation andsecretion of antiviral cytokines IFN-gamma and IL-2. In in vitro T-cell stimulation experiments, NS5A-derived antigens were modeled by synthetic peptides, recombinant proteins of various genotypes, and phages carrying exposed NS5A peptides. A novel immunomodulator Immunomax showed high adjuvant activity in DNA immunization. The data obtained indicate that the suggested DNA construct has a strong potential in the development of the gene vaccines against hepatitis C.