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Antiviral research

Antiviral research

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A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression

Published:25 November 2023 DOI: 10.1016/j.antiviral.2023.105763 PMID: 38008192
Li Yang , Ying Gong , Feifei Liu , Wuhong Chen , Xinran Wang , Guozhang Long , Heng Li , Fuling Xiao , MengJi Lu , Youhong Hu , Xiankun Tong , Jianping Zuo

Abstract

Development of new anti-hepatitis B virus (HBV) drugs that target viral capsid assembly is a very active research field. We identify a novel phthalazinone derivative, compound 5832, as a potent HBV inhibitor. In this study, we intend to elaborate the antiviral effect and mechanism of 5832 against HBV in vitro and in vivo. Compound 5832 treatment induces the formation of genome-free empty capsid by interfering with the core protein assembly domain, which significantly decreases the extracellular and intracellular HBV DNA. In the AAV-HBV transduced mouse model, 5832 suppresses serum HBV DNA after 4-week treatment, and decreases HBsAg and HBeAg levels. 5832 treatment also reduces intrahepatic HBV RNA, DNA and HBcAg levels. During the follow-up period after treatment withdrawal, serum antigen levels demonstrated no increase. We demonstrate 5832 treatment could active apoptotic signaling by elevating the expression of death receptor 5 (DR5), which participated in corresponding HBcAg-positive hepatocyte eradication. Phthalazinone derivative 5832 may serve as a promising anti-HBV drug candidate to improve the treatment options for chronic HBV infection.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Entecavir 142217-69-4 C12H15N5O3 572 suppliers $15.00-$4277.00
Entecavir 142217-69-4 C12H15N5O3 572 suppliers $15.00-$4277.00
Entecavir 142217-69-4 C12H15N5O3 572 suppliers $15.00-$4277.00
Entecavir 142217-69-4 C12H15N5O3 572 suppliers $15.00-$4277.00

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