New insights in the mechanism of the SARS-CoV-2 M<SUP>pro</SUP> inhibition by benzisoselenazolones and diselenides

doi:10.1038/s41598-024-75519-6

KMS > 免疫化学研究所

	New insights in the mechanism of the SARS-CoV-2 M^pro inhibition by benzisoselenazolones and diselenides
	Sancineto, Luca 1; Mangiavacchi, Francesca 1; Dabrowska, Agnieszka 2,3; Pacula-Miszewska, Agata J.4; Obieziurska-Fabisiak, Magdalena 4; Scimmi, Cecilia 1; Ceccucci, Veronica 1; Kong, Juan5 ; Zhao, Yao5 ; Ciancaleoni, Gianluca 6; Nascimento, Vanessa 7; Rizzuti, Bruno 8,9; Bortoli, Marco 10,11; Orian, Laura 12; Kula-Pacurar, Anna 2; Yang, Haitao5 ; Scianowski, Jacek 4; Lei, Ying5 ; Pyrc, Krzysztof 2; Santi, Claudio 1
	2024-10-21
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	14 期号:1
发表状态	已发表
DOI	10.1038/s41598-024-75519-6
摘要	Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (M-pro). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit M-pro; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated. Density functional theory calculations, molecular docking and molecular dynamics simulations were also used to elucidate the protein/drug interaction. Finally, a bio-organic model was established to study the reaction between selenorganic compounds and biologically relevant thiols to unveil possible metabolic pathways of such compounds. The overall results contribute to the identification of a series of novel Se-containing molecules active against SARS-CoV-2 and to the clarification of some important aspects in the mechanisms of action of such inhibitors targeting SARS-CoV-2 M-pro.
关键词	Benzisoselenazolones Diselenides SARS-CoV-2 main protease inhibitors Glutathione Ebselen
URL	查看原文
收录类别	PPRN.PPRN ; SCI
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001339991400098
出版者	NATURE PORTFOLIO
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/372981
专题	免疫化学研究所生命科学与技术学院免疫化学研究所_特聘教授组_饶子和组免疫化学研究所_公共科研平台_高通量筛选平台免疫化学研究所_PI研究组_杨海涛组
通讯作者	Lei, Ying; Pyrc, Krzysztof; Santi, Claudio
作者单位	1.Univ Perugia, Dept Pharmaceut Sci, Via Liceo 1, I-06100 Perugia, PG, Italy 2.Jagiellonian Univ, Malopolska Ctr Biotechnol, Virogenet Lab Virol, Gronostajowa 7a, PL-30 Krakow, Poland 3.Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Microbiol Dept, Gronostajowa 7, PL-30387 Krakow, Poland 4.Nicolaus Copernicus Univ, Fac Chem, Dept Organ Chem, 7 Gagarin St, Torun, Poland 5.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Univ Pisa, Dipartimento Chim & Chim Industriale DCCI, Via Giuseppe Moruzzi 13, I-56124 Pisa, Italy 7.Univ Fed Fluminense, Lab Sintese & Aplicacao Subst Supramol & Organoca, Dept Quim Organ, Outeiro Sao Joao Batista S-N, BR-24020141 Niteroi, RJ, Brazil 8.Univ Calabria, CNR, Dept Phys, SS Rende,NANOTEC, I-87036 Arcavacata Di Rende, CS, Italy 9.Univ Zaragoza, CSIC, Inst Biocomputat & Phys Complex Syst, Joint Unit GBsC,BIFI, Zaragoza 50018, Spain 10.Univ Oslo, Dept Chem, N-0315 Oslo, Norway 11.Univ Oslo, Hylleraas Ctr Quantum Mol Sci, N-0315 Oslo, Norway 12.Univ Padua, Dipartimento Sci Farmaceut, I-35131 Padua, Italy
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Sancineto, Luca,Mangiavacchi, Francesca,Dabrowska, Agnieszka,et al. New insights in the mechanism of the SARS-CoV-2 M^pro inhibition by benzisoselenazolones and diselenides[J]. SCIENTIFIC REPORTS,2024,14(1).
APA	Sancineto, Luca.,Mangiavacchi, Francesca.,Dabrowska, Agnieszka.,Pacula-Miszewska, Agata J..,Obieziurska-Fabisiak, Magdalena.,...&Santi, Claudio.(2024).New insights in the mechanism of the SARS-CoV-2 M^pro inhibition by benzisoselenazolones and diselenides.SCIENTIFIC REPORTS,14(1).
MLA	Sancineto, Luca,et al."New insights in the mechanism of the SARS-CoV-2 M^pro inhibition by benzisoselenazolones and diselenides".SCIENTIFIC REPORTS 14.1(2024).