Yutong Liu , Chang Wang , Huoyan Tong , Xi Zhou , Yuan Fang
{"title":"基于3C底物设计的肽在体内表现出抗病毒作用","authors":"Yutong Liu , Chang Wang , Huoyan Tong , Xi Zhou , Yuan Fang","doi":"10.1016/j.antiviral.2025.106185","DOIUrl":null,"url":null,"abstract":"<div><div>Enteroviruses are a large group of positive-sense single-stranded RNA viruses including numerous human pathogens such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. The diseases caused by these enteroviruses pose a significant threat to global public health. The 3C protein is a crucial protease in enteroviruses, responsible for cleaving the viral polyprotein into individual active proteins. This process is essential for viral replication and pathogenesis, making 3C an attractive target for the development of anti-enteroviral drugs. In this study, we designed and screened peptides based on the sequences of several substrates of the 3C protease, aiming to impact the function of the 3C protease and thereby exert antiviral effects. Ultimately, we obtained a peptide with good antiviral activity at the cellular level, which we named vp23. This peptide effectively disrupted the protease activity of 3C, provided significant <em>in vivo</em> protection against EV-A71, and possessed strong antiviral effects against multiple enteroviruses such as EV-A71, Coxsackievirus A16 (CV-A16), and Echovirus 11 (Echo 11). Taken together, our results suggest that targeting 3C proteases using rationally designed peptides is an effective antiviral strategy against enteroviruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"239 ","pages":"Article 106185"},"PeriodicalIF":4.5000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Peptides designed based on 3C substrates exhibit antiviral efficacy in vivo\",\"authors\":\"Yutong Liu , Chang Wang , Huoyan Tong , Xi Zhou , Yuan Fang\",\"doi\":\"10.1016/j.antiviral.2025.106185\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Enteroviruses are a large group of positive-sense single-stranded RNA viruses including numerous human pathogens such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. The diseases caused by these enteroviruses pose a significant threat to global public health. The 3C protein is a crucial protease in enteroviruses, responsible for cleaving the viral polyprotein into individual active proteins. This process is essential for viral replication and pathogenesis, making 3C an attractive target for the development of anti-enteroviral drugs. In this study, we designed and screened peptides based on the sequences of several substrates of the 3C protease, aiming to impact the function of the 3C protease and thereby exert antiviral effects. Ultimately, we obtained a peptide with good antiviral activity at the cellular level, which we named vp23. This peptide effectively disrupted the protease activity of 3C, provided significant <em>in vivo</em> protection against EV-A71, and possessed strong antiviral effects against multiple enteroviruses such as EV-A71, Coxsackievirus A16 (CV-A16), and Echovirus 11 (Echo 11). Taken together, our results suggest that targeting 3C proteases using rationally designed peptides is an effective antiviral strategy against enteroviruses.</div></div>\",\"PeriodicalId\":8259,\"journal\":{\"name\":\"Antiviral research\",\"volume\":\"239 \",\"pages\":\"Article 106185\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antiviral research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0166354225001111\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166354225001111","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Peptides designed based on 3C substrates exhibit antiviral efficacy in vivo
Enteroviruses are a large group of positive-sense single-stranded RNA viruses including numerous human pathogens such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. The diseases caused by these enteroviruses pose a significant threat to global public health. The 3C protein is a crucial protease in enteroviruses, responsible for cleaving the viral polyprotein into individual active proteins. This process is essential for viral replication and pathogenesis, making 3C an attractive target for the development of anti-enteroviral drugs. In this study, we designed and screened peptides based on the sequences of several substrates of the 3C protease, aiming to impact the function of the 3C protease and thereby exert antiviral effects. Ultimately, we obtained a peptide with good antiviral activity at the cellular level, which we named vp23. This peptide effectively disrupted the protease activity of 3C, provided significant in vivo protection against EV-A71, and possessed strong antiviral effects against multiple enteroviruses such as EV-A71, Coxsackievirus A16 (CV-A16), and Echovirus 11 (Echo 11). Taken together, our results suggest that targeting 3C proteases using rationally designed peptides is an effective antiviral strategy against enteroviruses.
期刊介绍:
Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.