Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells

IF 1.9 4区 医学 Q4 IMMUNOLOGY Microbiology and Immunology Pub Date : 2023-03-16 DOI:10.1111/1348-0421.13064
Chie Aoki-Utsubo, Puguh Indrasetiawan, Kento Fukano, Masamichi Muramatsu, Nina Artanti, Muhammad Hanafi, Hak Hotta, Masanori Kameoka
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引用次数: 2

Abstract

Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)–mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.

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阿门托黄酮通过抑制preS1与宿主细胞的结合抑制乙型肝炎病毒感染
乙型肝炎病毒(HBV)是导致慢性肝炎、肝硬化和肝细胞癌的主要原因。目前治疗慢性HBV感染的药物使用干扰素和核苷类似物;然而,它们的功效是有限的。因此,迫切需要开发用于HBV治疗的新型抗病毒药物。在这项研究中,我们鉴定了一种植物来源的多酚生物类黄酮,核黄素,作为一种新的抗HBV化合物。Amentoflavone治疗剂量依赖性地抑制HepG2-hNTCP-C4和原代人肝细胞PXB细胞的HBV易感细胞中的HBV感染。一项作用模式研究表明,核黄素抑制病毒进入步骤,但不抑制病毒内化和早期复制过程。核黄素抑制HBV颗粒和HBV前S1肽与HepG2-hNTCP-C4细胞的粘附。转运蛋白分析显示,核黄素部分抑制牛磺胆酸钠共转运多肽(NTCP)介导的胆汁酸的摄取。此外,还检测了各种核黄素类似物对HBV感染的HepG2-hNTCP-C4细胞产生HBs和HBe的影响。罗布斯塔黄酮表现出与核黄素和具有中等抗HBV活性的核黄素-7,4',4-三甲基醚衍生物(sciadopitysin)相当的抗HBV活性。Cupressuflavone或单体类黄酮芹菜素均未表现出抗病毒活性。Amentoflavone及其结构相关的双类黄酮可能为设计一种新的靶向NTCP的抗HBV药物抑制剂提供潜在的药物支架。
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来源期刊
Microbiology and Immunology
Microbiology and Immunology 医学-免疫学
CiteScore
5.20
自引率
3.80%
发文量
78
审稿时长
1 months
期刊介绍: Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses. Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.
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