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Here, GSH-modified ZnS NPs (GSH-ZnS NPs) were synthesized and their significant antiviral activity was demonstrated using the Arteriviridae family RNA virus, porcine reproductive and respiratory syndrome virus (PRRSV), as a model. Mechanistically, GSH-ZnS NPs were shown to reduce PRRSV-induced ROS production to prevent PRRSV multiplication, with no activating effect on the interferon (IFN) signal pathway, the first defense line against virus infection. Furthermore, isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of GSH-ZnS NP-treated cells revealed the involvement of numerous crucial proteins in virus proliferation, with vitronectin (VTN) being confirmed as an efficient PRRSV antagonist here. Furthermore, GSH-ZnS NPs were found to have potent antiviral effects on the Herpesviridae family DNA virus, pseudorabies virus (PRV), the Coronaviridae family positive-sense RNA virus, porcine epidemic diarrhea virus (PEDV), and the Rhabdoviridae family negative-stranded RNA virus, vesicular stomatitis virus (VSV), indicating their broad-spectrum antiviral activity against viruses from different families with various genome types. Overall, GSH-ZnS NP is a prospective candidate for the development of antiviral nanomaterials and may serve as a model for investigation of potential host restriction factors in combination with proteomics.<\/jats:p>","DOI":"10.1021\/acsabm.0c00332","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T03:03:40Z","timestamp":1592967820000},"page":"4809-4819","source":"Crossref","is-referenced-by-count":22,"title":["GSH-ZnS Nanoparticles Exhibit High-Efficiency and\nBroad-Spectrum Antiviral Activities via Multistep Inhibition Mechanisms"],"prefix":"10.1021","volume":"3","author":[{"given":"Yanrong","family":"Zhou","sequence":"first","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Tong","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liurong","family":"Fang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8210-0210","authenticated-orcid":true,"given":"Jiangong","family":"Liang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, P. R. 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