SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
Ilaria Frasson, Santina Quarta, Mariagrazia Ruvoletto, Alessandra Biasiolo, Monica Chinellato, Cristian Turato, Maristella Maggi, Laura Cendron, Sara N Richter, Patrizia Pontisso
{"title":"SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection.","authors":"Ilaria Frasson, Santina Quarta, Mariagrazia Ruvoletto, Alessandra Biasiolo, Monica Chinellato, Cristian Turato, Maristella Maggi, Laura Cendron, Sara N Richter, Patrizia Pontisso","doi":"10.1021/acsinfecdis.5c00145","DOIUrl":null,"url":null,"abstract":"<p><p>Recent research has proposed several host factors required for SARS-CoV-2 infection and involved in the inflammatory response. Among these, members of the human serpin family and PAR2 have been suggested to play a relevant role. As it has been shown that one of the multiple activities of protease inhibitor SerpinB3 is the activation of PAR2, we have modulated the expression of these two molecules on both human bronchial and hepatic cells and assessed cell surface Spike binding and SARS-CoV-2 infectivity. Our findings indicate that both SerpinB3 and PAR2 play a pivotal role in viral infection and downregulate the expression of interferon-γ, a cytokine with a well-known antiviral effect. These results underscore the potential of the SerpinB3-PAR2 axis as a target for antiviral therapy and provide support for addressing serpins as targets for this purpose.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-05-23","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.5c00145","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Recent research has proposed several host factors required for SARS-CoV-2 infection and involved in the inflammatory response. Among these, members of the human serpin family and PAR2 have been suggested to play a relevant role. As it has been shown that one of the multiple activities of protease inhibitor SerpinB3 is the activation of PAR2, we have modulated the expression of these two molecules on both human bronchial and hepatic cells and assessed cell surface Spike binding and SARS-CoV-2 infectivity. Our findings indicate that both SerpinB3 and PAR2 play a pivotal role in viral infection and downregulate the expression of interferon-γ, a cytokine with a well-known antiviral effect. These results underscore the potential of the SerpinB3-PAR2 axis as a target for antiviral therapy and provide support for addressing serpins as targets for this purpose.

SerpinB3/蛋白酶激活受体-2轴对SARS CoV-2感染至关重要
最近的研究提出了SARS-CoV-2感染所需的几种宿主因子,并参与炎症反应。其中,人类serpin家族成员和PAR2被认为发挥了相关作用。由于已经证明蛋白酶抑制剂SerpinB3的多种活性之一是PAR2的激活,我们已经调节了这两个分子在人支气管和肝细胞上的表达,并评估了细胞表面刺突结合和SARS-CoV-2的传染性。我们的研究结果表明,SerpinB3和PAR2在病毒感染中发挥关键作用,并下调干扰素-γ的表达,干扰素-γ是一种众所周知的抗病毒作用的细胞因子。这些结果强调了SerpinB3-PAR2轴作为抗病毒治疗靶点的潜力,并为将SerpinB3-PAR2轴作为抗病毒治疗靶点提供了支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信