Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx

He, Jingjing; Wu, Jingwen; Chen, Jingwen; Zhang, Shenyan; Guo, Yifei; Zhang, Xueyun; Han, Jiajia; Zhang, Yao; Guo, Yue; Lin, Yanxue; Yu, Weien; Kong, Yide; Shen, Zhongliang; Mao, Richeng; Zhang, Jiming

doi:10.3390/molecules27155000

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…Accordingly, Estradiol benzoate has been reported in numerous instances where it has been used as a competitive drug to inhibit viral growth. The antiviral activity of Estradiol benzoate against SARS-CoV-2 and the hepatitis B virus has been previously reported [ 52 , 55 , 56 ]. By binding to and disrupting the six-helix (6-HB) fusion core of SARS-CoV-2 S protein, Estradiol benzoate is able to block viral entry [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

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Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Alsaady,

Bajrai,

Alandijany

et al. 2023

Viruses

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The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.

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Section: Resultsmentioning

confidence: 99%

“…By binding to and disrupting the six-helix (6-HB) fusion core of SARS-CoV-2 S protein, Estradiol benzoate is able to block viral entry [ 56 ]. Using HepG2.2.15 cells and HepG2 transfected cells as a cellular model of HBV replication, it was also found that Estradiol benzoate inhibited HBV replication and transcription [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Alsaady,

Bajrai,

Alandijany

et al. 2023

Viruses

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Targeting hepatitis B virus cccDNA levels: Recent progress in seeking small molecule drug candidates

Wang

Zhao

et al. 2023

Drug Discovery Today

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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis

Schollmeier

Glitscher

Hildt

2023

IJMS

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The hepatitis B virus (HBV) counts as a major global health problem, as it presents a significant causative factor for liver-related morbidity and mortality. The development of hepatocellular carcinomas (HCC) as a characteristic of a persistent, chronic infection could be caused, among others, by the pleiotropic function of the viral regulatory protein HBx. The latter is known to modulate an onset of cellular and viral signaling processes with emerging influence in liver pathogenesis. However, the flexible and multifunctional nature of HBx impedes the fundamental understanding of related mechanisms and the development of associated diseases, and has even led to partial controversial results in the past. Based on the cellular distribution of HBx—nuclear-, cytoplasmic- or mitochondria-associated—this review encompasses the current knowledge and previous investigations of HBx in context of cellular signaling pathways and HBV-associated pathogenesis. In addition, particular focus is set on the clinical relevance and potential novel therapeutic applications in the context of HBx.

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Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx

Cited by 4 publications

References 43 publications

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Targeting hepatitis B virus cccDNA levels: Recent progress in seeking small molecule drug candidates

Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis

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