کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6140907 | 1594259 | 2013 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterizations of HCV NS5A replication complex inhibitors
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Characterizations of HCV NS5A replication complex inhibitors Characterizations of HCV NS5A replication complex inhibitors](/preview/png/6140907.png)
چکیده انگلیسی
The hepatitis C virus NS5A protein is an established and clinically validated target for antiviral intervention by small molecules. Characterizations are presented of compounds identified as potent inhibitors of HCV replication to provide insight into structural elements that interact with the NS5A protein. UV-activated cross linking and affinity isolation was performed with one series to probe the physical interaction between the inhibitors and the NS5A protein expressed in HCV replicon cells. Resistance mapping with the second series was used to determine the functional impact of specific inhibitor subdomains on the interaction with NS5A. The data provide evidence for a direct high-affinity interaction between these inhibitors and the NS5A protein, with the interaction dependent on inhibitor stereochemistry. The functional data supports a model of inhibition that implicates inhibitor binding by covalently combining distinct pharmacophores across an NS5A dimer interface to achieve maximal inhibition of HCV replication.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 444, Issues 1â2, September 2013, Pages 343-354
Journal: Virology - Volume 444, Issues 1â2, September 2013, Pages 343-354
نویسندگان
Donald R. O'Boyle II, Jin-Hua Sun, Peter T. Nower, Julie A. Lemm, Robert A. Fridell, Chunfu Wang, Jeffrey L. Romine, Makonen Belema, Van N. Nguyen, Denis R. St. Laurent, Michael Serrano-Wu, Lawrence B. Snyder, Nicholas A. Meanwell, David R. Langley,