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SB9200,一种新型先天免疫激动剂,对耐药 HCV 变异体显示出强大的抗病毒活性。

SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants.

机构信息

The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.

Spring Bank Pharmaceuticals, Milford, Massachusetts.

出版信息

J Med Virol. 2017 Sep;89(9):1620-1628. doi: 10.1002/jmv.24809. Epub 2017 May 23.

Abstract

SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus, and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus. Using the HCV capture-fusion assay, we show that SB 9200 is active against diverse HCV genotypes and is also effective against HCV derived from patients who relapse following direct-acting antiviral treatment, including viruses containing known NS5A resistance-associated sequences. These data confirm the broad antiviral activity of SB 9200 and indicate that it may have clinical utility in HCV patients who have failed to respond to current antiviral regimens.

摘要

SB 9200 是一种新型的、首创的先天免疫调节剂,据信通过激活 RIG-I 和 NOD2 途径发挥作用。SB 9200 对包括丙型肝炎病毒 (HCV)、诺如病毒、呼吸道合胞病毒和流感在内的 RNA 病毒具有广谱抗病毒活性,并已证明在体外和体内对乙型肝炎病毒 (HBV)具有活性。在慢性 HCV 感染患者的 I 期临床试验中,SB 9200 已被证明可将 HCV RNA 降低多达 1.9 对数级。在这里,我们证明了 SB 9200 对 HCV 复制子系统和患者来源病毒的抗病毒活性。使用 HCV 捕获-融合测定法,我们表明 SB 9200 对多种 HCV 基因型有效,并且对直接作用抗病毒治疗后复发的患者来源的 HCV 也有效,包括含有已知 NS5A 耐药相关序列的病毒。这些数据证实了 SB 9200 的广泛抗病毒活性,并表明它可能对未能对现有抗病毒方案产生反应的 HCV 患者具有临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/408e/5513743/1f902e9c0872/nihms861999f1.jpg

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