Acetophenone 4-nitrophenylhydrazone inhibits Hepatitis B virus replication by modulating capsid assembly

Yamasaki, Makari; Matsuda, Norie; Matoba, Kazuaki; Kondo, Shu; Kanegae, Yumi; Saito, Izumu; Nomoto, Akio

doi:10.1016/j.virusres.2021.198565

Cited by 6 publications

(2 citation statements)

References 34 publications

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“…Another chemical structure, ANPH, containing a N-N bond was identified recently [100]. ANPH is an acetophenone-derived hydrazone (HZ) found by HTS using the HBV103-AdV system in Huh-7 cells (EC 50 , 0.83 µM).…”

Section: Hydrazonesmentioning

confidence: 99%

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy

Kim

Lee

et al. 2021

Molecules

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Hepatitis B virus (HBV) is a major causative agent of human hepatitis. Its viral genome comprises partially double-stranded DNA, which is complexed with viral polymerase within an icosahedral capsid consisting of a dimeric core protein. Here, we describe the effects of capsid assembly modulators (CAMs) on the geometric or kinetic disruption of capsid construction and the virus life cycle. We highlight classical, early-generation CAMs such as heteroaryldihydropyrimidines, phenylpropenamides or sulfamoylbenzamides, and focus on the chemical structure and antiviral efficacy of recently identified non-classical CAMs, which consist of carboxamides, aryl ureas, bithiazoles, hydrazones, benzylpyridazinones, pyrimidines, quinolines, dyes, and antimicrobial compounds. We summarize the therapeutic efficacy of four representative classical compounds with data from clinical phase 1 studies in chronic HBV patients. Most of these compounds are in phase 2 trials, either as monotherapy or in combination with approved nucleos(t)ides drugs or other immunostimulatory molecules. As followers of the early CAMs, the therapeutic efficacy of several non-classical CAMs has been evaluated in humanized mouse models of HBV infection. It is expected that these next-generation HBV CAMs will be promising candidates for a series of extended human clinical trials.

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Section: Hydrazonesmentioning

confidence: 99%

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy

Kim

Lee

et al. 2021

Molecules

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“…Recently, by screening an in-house compound library, a new molecular motif; N-(4nitrophenyl)-1-phenylethanone hydrazone (Table 2) was identified as the inhibitor targeting HBV replication by targeting its capsid assembly [138]. This compound accelerates the assembly and induces the formation of empty viral particles lacking genomic RNA.…”

Section: Hepatitis B Virus Assembly Inhibitorsmentioning

confidence: 99%

Targeting the Virus Capsid as a Tool to Fight RNA Viruses

Hozáková

Vokatá

Ruml

et al. 2022

Viruses

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Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses.

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Emerging Therapies for Chronic Hepatitis B and the Potential for a Functional Cure

Chang

Liaw

2023

Drugs

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Acetophenone 4-nitrophenylhydrazone inhibits Hepatitis B virus replication by modulating capsid assembly

Cited by 6 publications

References 34 publications

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy

Targeting the Virus Capsid as a Tool to Fight RNA Viruses

Emerging Therapies for Chronic Hepatitis B and the Potential for a Functional Cure

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