کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8297665 | 1536778 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives
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کلمات کلیدی
HCVppHCVccVSVHBSMOI - MECSA - ایالات مؤتلفهٔ آمریکاinterferon - اینترفرونIFN - اینترفرون هاCompound - ترکیبcyclosporin A - سیکلوسپورین AScreening - غربالگریNatural product - فراورده طبیعیHepatitis C virus - هپاتیت سیHCV - هپاتیت سیEntry - ورودVesicular stomatitis virus - ویروس vesicular stomatitismultiplicity of infection - چندین عفونت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma. Although various classes of anti-HCV agents have been under clinical development, most of these agents target RNA replication in the HCV life cycle. To achieve a more effective multidrug treatment, the development of new, less expensive anti-HCV agents that target a different step in the HCV life cycle is needed. We prepared an in-house natural product library consisting of compounds derived from fungal strains isolated from seaweeds, mosses, and other plants. A cell-based functional screening of the library identified sulochrin as a compound that decreased HCV infectivity in a multi-round HCV infection assay. Sulochrin inhibited HCV infection in a dose-dependent manner without any apparent cytotoxicity up to 50 μM. HCV pseudoparticle and trans-complemented particle assays suggested that this compound inhibited the entry step in the HCV life cycle. Sulochrin showed anti-HCV activities to multiple HCV genotypes 1a, 1b, and 2a. Co-treatment of sulochrin with interferon or a protease inhibitor telaprevir synergistically augmented their anti-HCV effects. Derivative analysis revealed anti-HCV compounds with higher potencies (IC50 < 5 μM). This is the first report showing an antiviral activity of methoxybenzoate derivatives. Thus, sulochrin derivatives are anti-HCV lead compounds with a new mode of action.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 4, 1 November 2013, Pages 515-520
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 4, 1 November 2013, Pages 515-520
نویسندگان
Syo Nakajima, Koichi Watashi, Shinji Kamisuki, Senko Tsukuda, Kenji Takemoto, Mami Matsuda, Ryosuke Suzuki, Hideki Aizaki, Fumio Sugawara, Takaji Wakita,