دانلود رایگان مقاله مکانیسم ضد ویروسی پلیمرهای اسید نوکلئیک برای درمان هپاتیت B و D

Abstract

Antiviral polymers are a well-studied class of broad spectrum viral attachment/entry inhibitors whose activity increases with polymer length and with increased amphipathic (hydrophobic) character. The newest members of this class of compounds are nucleic acid polymers whose activity is derived from the sequence independent properties of phosphorothioated oligonucleotides as amphipathic polymers. Although the antiviral mechanisms and broad spectrum antiviral activity of nucleic acid polymers mirror the functionality of other members of this class, they exert in addition a unique post entry activity in hepatitis B infection which inhibits the release of HBsAg from infected hepatocytes. This review provides a general overview of the antiviral polymer class with a focus on nucleic acid polymers and their development as therapeutic agents for the treatment of hepatitis B/hepatitis D. This article forms part of a symposium in Antiviral Research on ‘‘An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.’’

9. Future perspectives

Given the established therapeutic activity of NAPs against HBV and HDV infection in vivo and in several preliminary clinical investigations, the elucidation of the molecular basis for the clearance of HBsAg and HDV RNA from the blood by NAPs may lead to an improved understanding of the HBV and HDV lifecycle. Investigations into the post-entry antiviral mechanisms of NAPs in HBV and HBV/HDV infections are underway in earnest. Notwithstanding this, the current pattern of antiviral effects of NAPs in vivo and in patients support the general hypothesis that NAPs act to block HBsAg release from infected hepatocytes (perhaps selectively for SVPs) by some non-immunostimulatory mechanism inside infected cells and demonstrate that NAP therapy can achieve substantial reduction or clearance of serum HBsAg in chronic HBV infection.