{"title":"通过靶向病毒 2C 蛋白发现 A-967079 作为肠病毒 D68 的抗病毒药物","authors":"Haozhou Tan, Brian Pollard, Kan Li, Jun Wang","doi":"10.1021/acsinfecdis.4c00678","DOIUrl":null,"url":null,"abstract":"<p><p>Enterovirus D68 (EV-D68) has had several outbreaks worldwide, yet no FDA-approved antiviral is available for treating this viral infection. EV-D68 infection typically leads to respiratory illnesses and, in severe cases, can cause neurological complications and even death, particularly in children. This study identified a small molecule, A-967079, as an EV-D68 antiviral through phenotypical screening. A-967079 has shown potent and broad-spectrum antiviral activity with a high selectivity index against multiple strains of EV-D68. Pharmacological characterization of the mechanism of action involving time-of-addition, resistance selection, and differential scanning fluorimetry assays suggests that viral 2C protein is the drug target. Overall, A-967079 represents a promising candidate for further development as an EV-D68 antiviral.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"4327-4336"},"PeriodicalIF":4.0000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery of A-967079 as an Enterovirus D68 Antiviral by Targeting the Viral 2C Protein.\",\"authors\":\"Haozhou Tan, Brian Pollard, Kan Li, Jun Wang\",\"doi\":\"10.1021/acsinfecdis.4c00678\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Enterovirus D68 (EV-D68) has had several outbreaks worldwide, yet no FDA-approved antiviral is available for treating this viral infection. EV-D68 infection typically leads to respiratory illnesses and, in severe cases, can cause neurological complications and even death, particularly in children. This study identified a small molecule, A-967079, as an EV-D68 antiviral through phenotypical screening. A-967079 has shown potent and broad-spectrum antiviral activity with a high selectivity index against multiple strains of EV-D68. Pharmacological characterization of the mechanism of action involving time-of-addition, resistance selection, and differential scanning fluorimetry assays suggests that viral 2C protein is the drug target. Overall, A-967079 represents a promising candidate for further development as an EV-D68 antiviral.</p>\",\"PeriodicalId\":17,\"journal\":{\"name\":\"ACS Infectious Diseases\",\"volume\":\" \",\"pages\":\"4327-4336\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-12-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acsinfecdis.4c00678\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acsinfecdis.4c00678","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Discovery of A-967079 as an Enterovirus D68 Antiviral by Targeting the Viral 2C Protein.
Enterovirus D68 (EV-D68) has had several outbreaks worldwide, yet no FDA-approved antiviral is available for treating this viral infection. EV-D68 infection typically leads to respiratory illnesses and, in severe cases, can cause neurological complications and even death, particularly in children. This study identified a small molecule, A-967079, as an EV-D68 antiviral through phenotypical screening. A-967079 has shown potent and broad-spectrum antiviral activity with a high selectivity index against multiple strains of EV-D68. Pharmacological characterization of the mechanism of action involving time-of-addition, resistance selection, and differential scanning fluorimetry assays suggests that viral 2C protein is the drug target. Overall, A-967079 represents a promising candidate for further development as an EV-D68 antiviral.
期刊介绍：
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
