{"title":"Discovery of potent measles virus fusion inhibitor peptides via structure-guided derivatization†","authors":"Ziwei Gao, Jiei Sasaki, Tateki Suzuki, Tomoaki Suzuki, Yuki Miwa, Shinsuke Sando, Takao Hashiguchi and Jumpei Morimoto","doi":"10.1039/D4MD01006J","DOIUrl":null,"url":null,"abstract":"<p >Fusion inhibitor peptide (FIP), a short peptide known as a measles virus (MeV) infection inhibitor, inhibits membrane fusion between the viral envelope of MeV and the host cell membrane. Therefore, FIP is potentially useful as a drug candidate for treating MeV infection, but improvement of inhibitory activity is desirable. In this study, we conducted a structure–activity relationship study of FIP and, based on the result and the previously reported crystal structure of the complex, we designed FIP derivatives. From a series of derivatives, we discovered an FIP derivative with a strong inhibitory activity (IC<small><sub>50</sub></small> = 210 nM) derived from the enhanced binding affinity (<em>K</em><small><sub>D</sub></small> = 6.6 nM) to the MeV fusion protein.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1619-1625"},"PeriodicalIF":3.5970,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799930/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"MedChemComm","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2025/md/d4md01006j","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Fusion inhibitor peptide (FIP), a short peptide known as a measles virus (MeV) infection inhibitor, inhibits membrane fusion between the viral envelope of MeV and the host cell membrane. Therefore, FIP is potentially useful as a drug candidate for treating MeV infection, but improvement of inhibitory activity is desirable. In this study, we conducted a structure–activity relationship study of FIP and, based on the result and the previously reported crystal structure of the complex, we designed FIP derivatives. From a series of derivatives, we discovered an FIP derivative with a strong inhibitory activity (IC50 = 210 nM) derived from the enhanced binding affinity (KD = 6.6 nM) to the MeV fusion protein.
期刊介绍:
Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry.
In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.