Identification of peptide-based hepatitis B virus capsid inhibitors based on the viral core protein

被引：0

作者：

Fujimoto, Junko ^{[1
]}

Kawahara, Kazutoshi ^{[2
]}

Takeda, Kazuma ^{[1
]}

Takeo, Sayuri ^{[3
]}

Sato, Kohei ^{[1
,2
,4
]}

Nakashima, Kenji ^{[5
]}

Mase, Nobuyuki ^{[1
,2
,4
]}

Yokoyama, Masaru ^{[6
]}

Suzuki, Tetsuro ^{[5
]}

Narumi, Tetsuo ^{[1
,2
,3
,4
]}

机构：

[1] Shizuoka Univ, Fac Engn, Dept Appl Chem & Biochem Engn, 3-5-1 Johoku, Hamamatsu, Shizuoka 4328561, Japan

[2] Shizuoka Univ, Grad Sch Integrated Sci & Technol, Dept Engn, 3-5-1 Johoku, Hamamatsu, Shizuoka 4328561, Japan

[3] Shizuoka Univ, Grad Sch Med Photon, 3-5-1 Johoku Naka Ku, Hamamatsu, Shizuoka, Japan

[4] Shizuoka Univ, Res Inst Green Sci & Technol, 3-5-1 Johoku, Hamamatsu, Shizuoka 4328561, Japan

[5] Hamamatsu Univ Sch Med, Dept Microbiol & Immunol, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan

[6] Natl Inst Infect Dis, Pathogen Genom Ctr, 4-7-1 Gakuen, Musashimurayama, Tokyo, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2025年 / 117卷

关键词：

Hepatitis B virus (HBV); Capsid assembly inhibitors; Peptide library screening; Molecular dynamics simulations; REPLICATION; GLS4;

D O I：

10.1016/j.bmcl.2024.130054

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页数：6

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