A Short Peptide Inhibitor of Measles Virus Fusion Protein that Exhibits Passive Membrane Permeability

IF 3.4 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-07-28 DOI:10.1002/cmdc.202500532

Ziwei Gao, Jiei Sasaki, Tateki Suzuki, Shinsuke Sando, Takao Hashiguchi, Jumpei Morimoto

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Abstract

In this study, a passively membrane-permeable short peptide inhibitor targeting the measles virus fusion protein (MeV-F) is reported. Measles virus (MeV) is highly contagious, yet no approved antiviral drugs are currently available. MeV-F plays a crucial role in viral infection, making it an attractive target for drug development. The fusion inhibitor peptide (FIP) is a well-known short peptide that binds to MeV-F and prevents its structural rearrangement. However, improving both inhibitory activity and passive membrane permeability is essential for developing orally available MeV-F inhibitors. Herein, FIP derivatives are explored through hydrogen-to-fluorine substitution and a derivative with enhanced inhibitory activity (IC₅₀ = 90 nM) and passive membrane permeability (P_e = 1.4 × 10^–6 cm s⁻¹) was identified. This study highlights the potential of the long-studied fusion inhibitor peptide as a promising lead compound for the development of orally available drugs against measles infection.

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麻疹病毒融合蛋白的短肽抑制剂表现出被动膜渗透性。

本研究报道了一种针对麻疹病毒融合蛋白（MeV-F）的被动膜透性短肽抑制剂。麻疹病毒（MeV）具有高度传染性，但目前尚无批准的抗病毒药物可用。MeV-F在病毒感染中起着至关重要的作用，使其成为药物开发的一个有吸引力的靶点。融合抑制肽（FIP）是一种众所周知的与MeV-F结合并阻止其结构重排的短肽。然而，提高抑制活性和被动膜通透性对于开发口服MeV-F抑制剂至关重要。本文通过氢-氟置换对FIP衍生物进行了探索，并鉴定出具有增强抑制活性（IC50 = 90 nM）和被动膜透性（Pe = 1.4 × 10-6 cm s-1）的衍生物。这项研究强调了长期研究的融合抑制剂肽作为开发口服抗麻疹感染药物的有希望的先导化合物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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