Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV lifecycle
Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV lifecycle
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DOI：
10.1016/j.antiviral.2014.03.017
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发表时间：
2014-06-01
影响因子：
7.6
通讯作者：
Labonte, Patrick
中科院分区：
文献类型：
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作者：
Blanchet, Matthieu;Sureau, Camille;Labonte, Patrick
全世界约有2.4亿人慢性感染乙肝病毒，其中1500万至2000万人同时感染丁型肝炎病毒(HDV)。目前可用的治疗方法并不完全有效，而且往往与重要的副作用和耐药性的产生有关。使用preS1特异性脂肽靶向乙肝病毒/HDV进入步骤似乎是一种有希望的策略，可以阻止乙肝病毒和HDV的病毒进入(Grigon等人，2005年；Petersen等人，2008年)。最近，人牛磺胆酸钠共转运多肽(HNTCP)被鉴定为一种功能性的、前S1特异性的乙肝病毒和丁型肝炎病毒受体。这一突破性的发现为治疗慢性乙肝和丁型肝炎病毒感染开辟了一条非常有希望的途径。在这里，我们使用HDV体外感染模型，以表达hNTCP的Huh7细胞系为基础，研究了FDA批准的对hNTCP细胞功能有抑制作用的治疗药物损害病毒进入的能力。我们证明了FDA批准的三种分子厄贝沙坦、依折麦布和利托那韦在体外改变HDV感染的潜力。(C)2014爱思唯尔B.V.保留所有权利。
Worldwide there are approximately 240 million individuals chronically infected with the hepatitis B virus (HBV), including 15-20 million coinfected with the hepatitis delta virus (HDV). Treatments available today are not fully efficient and often associated to important side effects and development of drug resistance. Targeting the HBV/HDV entry step using preS1-specific lipopeptides appears as a promising strategy to block viral entry for both HBV and HDV (Gripon et al., 2005; Petersen et al., 2008). Recently, the human Sodium Taurocholate Cotransporting Polypeptide (hNTCP) has been identified as a functional, preS1-specific receptor for HBV and HDV. This groundbreaking discovery has opened a very promising avenue for the treatment of chronic HBV and HDV infections. Here we investigated the ability of FDA approved therapeutics with documented inhibitory effect on hNTCP cellular function to impair viral entry using a HDV in vitro infection model based on a hNTCP-expressing Huh7 cell line. We demonstrate the potential of three FDA approved molecules, irbesartan, ezetimibe, and ritonavir, to alter HDV infection in vitro. (C) 2014 Elsevier B.V. All rights reserved.