کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5822019 1557828 2015 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of novel respiratory syncytial virus inhibitors identified by high throughput screen
ترجمه فارسی عنوان
تشخیص مهارکننده های جدیدی از ویروس های تنفسی سونسیتی سیتالی که با استفاده از صفحه نمایش با توان بالا شناخته می شوند
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
چکیده انگلیسی
Respiratory Syncytial Virus (RSV) is a major cause of lower respiratory tract infections with no effective treatment available. Finding novel inhibitors of RSV is an important first step towards developing an efficacious RSV therapy. Here we report the characterization of three novel classes of RSV replication inhibitors identified through a high throughput RSV replicon screen of ∼1 million compounds in the AstraZeneca compound collection. These inhibitors, cpd 1, 2, and 3, specifically targeted RSV and were not active against other viruses tested. Resistance selection in RSV A2 with cpd 1 identified escape viruses with mutations mapped to the RSV L protein, an RNA-dependent RNA polymerase (Y1631C and I1413T). Recombinant RSV containing the L Y1631C substitution conferred resistance towards cpd 1, suggesting that the RSV polymerase is the target of this inhibitor. Interestingly, cpd 3, a nucleoside analog, induced a single resistant mutation in the P protein (D231V), indicating a novel mode of action not previously reported. cpd 2 affected host cell cycle and no frequent mutation was isolated following resistance selection, suggesting its possible involvement of a host-targeted mechanism. Taken together, we have identified three novel RSV inhibitors with different modes of action, providing new chemistry starting points for the discovery and development of future RSV therapeutic treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 115, March 2015, Pages 71-74
نویسندگان
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