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REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection.
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2018-10-05 , DOI: 10.1021/acsinfecdis.8b00156
Andrew Vaillant 1
Affiliation  

Nucleic acid polymers (NAPs) are broad spectrum antiviral agents whose antiviral activity in hepatitis B virus (HBV) infection is derived from their ability to block the release of the hepatitis B virus surface antigen (HBsAg). This pharmacological activity blocks replenishment of HBsAg in the circulation, allowing host mediated clearance. This effect has important clinical significance as the clearance of circulating HBsAg dramatically potentiates the ability of immunotherapies to restore functional control of HBV infection which persists after antiviral therapy is removed. These effects are reproducible in preclinical evaluations and in several clinical trials that have evaluated the activity of the lead NAP, REP 2139, in monotherapy and in combination with immunotherapy in hepatitis B e antigen (HBeAg) negative and HBeAg positive HBV infection and also in HBeAg negative HBV/hepatitis D virus (HDV) coinfection. These antiviral effects of REP 2139 are achieved in the absence of any direct immunostimulatory effect in the liver and also without any discernible direct interaction with viral components. The search for the host protein interaction with NAPs that drives their antiviral effects is ongoing, and the interaction targeted by REP 2139 within infected cells has not yet been elucidated. This article provides an updated review of available data on the effects of REP 2139 in HBV and HDV infection and the ability of REP 2139-based combination therapy to achieve functional control of HBV and HDV infection in patients.

中文翻译:

REP 2139:抗病毒机制及其在实现HBV和HDV感染功能控制中的应用。

核酸聚合物(NAP)是广谱抗病毒药物,其对乙型肝炎病毒(HBV)感染的抗病毒活性源自其阻断乙型肝炎病毒表面抗原(HBsAg)释放的能力。这种药理活性阻止循环中HBsAg的补充,从而允许宿主介导的清除。该作用具有重要的临床意义,因为清除循环中的HBsAg可显着增强免疫疗法恢复对HBV感染的功能控制的能力,该功能在去除抗病毒治疗后仍然有效。在临床前评估和一些评估NAP前导REP 2139活性的临床试验中,这些效果是可重现的。单一疗法联合免疫疗法可治疗乙型肝炎e抗原(HBeAg)阴性和HBeAg阳性HBV感染,以及HBeAg阴性HBV / D型肝炎病毒(HDV)合并感染。REP 2139的这些抗病毒作用是在肝脏中不存在任何直接免疫刺激作用且与病毒成分之间没有任何明显的直接相互作用的情况下实现的。寻找宿主蛋白与驱动其抗病毒作用的NAP相互作用的工作正在进行中,并且尚未阐明REP 2139在感染细胞内靶向的相互作用。本文提供了有关REP 2139在HBV和HDV感染中的作用以及基于REP 2139的联合疗法对患者进行HBV和HDV感染的功能控制的能力的最新数据的最新综述。
更新日期:2018-09-10
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