کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9287106 | 1227397 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of native hepatitis C virus replicase by nucleotide and non-nucleoside inhibitors
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
NS5BRNA polymerase - آرانای پلیمراز، RNA پلیمراز Cell fractionation - تجزیه سلولMembrane protein complex - مجتمع پروتئین غشاییAllosteric inhibitor - مهار کننده آلوستریکnon-nucleoside inhibitor - مهار کننده غیر نوکلئیدیNucleoside - هسته ایReplication - همانندسازی hepatitis - هپاتیتReplicase - کپی رایت
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A number of nucleotide and non-nucleoside inhibitors of HCV polymerase are currently under investigation as potential antiviral agents to treat HCV-infected patients. HCV polymerase is part of a replicase complex including the polymerase subunit NS5B together with other viral and host proteins and viral RNA. The RNA synthesis activity of the native replicase complex was inhibited by 3â²-deoxy-CTP, a chain-terminating nucleotide analog, but not inhibited by non-nucleoside NS5B polymerase inhibitors of three different structural classes. The HCV replicase was also resistant to heparin, a broad-spectrum, RNA-competitive polymerase inhibitor. Prebinding of the recombinant NS5B protein with a RNA template rendered the polymerase largely resistant to the inhibition by heparin and the non-nucleoside inhibitors, but did not affect the inhibitory potency of 3â²-deoxy-CTP. Therefore, the HCV replicase showed a similar pattern of inhibitor sensitivity as compared to RNA-bound NS5B. These results suggest that the native HCV replicase complex represents a stable and productive polymerase-RNA complex. The allosteric non-nucleoside NS5B polymerase inhibitors are inactive against established HCV replicase but may function antagonistically with the formation of a productive enzyme-template complex.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 332, Issue 1, 5 February 2005, Pages 8-15
Journal: Virology - Volume 332, Issue 1, 5 February 2005, Pages 8-15
نویسندگان
Han Ma, Vincent Leveque, Anniek De Witte, Weixing Li, Than Hendricks, Saundra M. Clausen, Nick Cammack, Klaus Klumpp,