SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection

Li, Xiaofang; Nakashima, Kenji; Ito, Masahiko; Matsuda, Mami; Chida, Takeshi; Sekihara, Kazumasa; Takahashi, Hirotaka; Kato, Takanobu; Sawasaki, Tatsuya; Suzuki, Tetsuro

doi:10.1016/j.antiviral.2023.105756

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…Each peptide was added during cell-free HBV Cp synthesis using wheat germ lysates and capsid assembly; HBV capsids were electrophoresed on native agarose gel and HBV capsids were detected by Western blotting (Figure 2A "Native capsid assay"). 23 Of the 72 peptides tested, peptides 19Ac and 20Ac significantly inhibited HBV-capsid formation (Figure 2B).…”

Section: Resultsmentioning

confidence: 92%

Identification of Peptide-Based Hepatitis B Virus Capsid Inhibitors Based on the Viral Core Protein

Kawahara,

Fujimoto,

Takeo

et al. 2024

Preprint

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In this study, we have identified two novel peptides, 19Ac (comprising residues 91-105) and 20Ac (encompassing residues 96-110), from a systematically designed peptide library based on the Hepatitis B virus (HBV) core protein, that inhibit the assembly of HBV capsid. Peptide 20Ac exhibited about twofold the inhibitory potency of 19Ac and proved effective against both standard and morphothiadin (GLS4)-resistant HBV strains. Molecular dynamics simulations revealed that despite their overlapping sequence, 19Ac and 20Ac bonded to different regions of the core protein, thereby inhibiting capsid assembly through distinct mechanisms. These peptides could serve as valuable seed compounds for the further development of HBV capsid inhibitors, including GLS4-resistant strains.

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Section: Resultsmentioning

confidence: 92%

Identification of Peptide-Based Hepatitis B Virus Capsid Inhibitors Based on the Viral Core Protein

Kawahara,

Fujimoto,

Takeo

et al. 2024

Preprint

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Novel mechanistic insights – A brand new Era for anti-HBV drugs

Lyu,

Qin,

et al. 2024

European Journal of Medicinal Chemistry

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FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation

Liu,

Ito,

Sakai

et al. 2024

Front. Microbiol.

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Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases and is known to induce endoplasmic reticulum (ER) stress, which alters cellular homeostasis and metabolic processes. While ER stress is implicated in HCV-related diseases, its precise role remains unclear. This study identifies fibroblast growth factor 21 (FGF21) as a key host factor significantly upregulated by HCV infection. Mechanistic analyses reveal that the activation of the FGF21 promoter by HCV is primarily mediated by the transcription factor ATF4, which is upregulated through the phosphorylation of eIF2α induced by ER stress. Additionally, CREBH activation further enhances ATF4 expression, contributing to increased FGF21 levels. TRIB3, upregulated by ATF4, acts as a negative regulator of FGF21 expression. The study also identifies FGF21-dependent upregulation of SOCS2 and TRIM31 in HCV-infected cells. SOCS2 contributes to the suppression of type 1 interferon signaling, aiding viral persistence, while TRIM31 promotes the degradation of the tumor suppressor protein TSC, activating the mTORC1 pathway and potentially promoting liver cell proliferation. These findings suggest that FGF21 upregulation in HCV-infected cells may play a role in both immune response regulation and cell proliferation, contributing to sustained viral infection and disease progression.

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SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection

Cited by 3 publications

References 41 publications

Identification of Peptide-Based Hepatitis B Virus Capsid Inhibitors Based on the Viral Core Protein

Identification of Peptide-Based Hepatitis B Virus Capsid Inhibitors Based on the Viral Core Protein

Novel mechanistic insights – A brand new Era for anti-HBV drugs

FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation

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