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Thus, active molecules targeting multiple steps in SARS\u2010CoV\u20102 lifecycle are highly wanted. Herein we explored the in silico capability of silibinin from <jats:italic>Silybum marianum<\/jats:italic> to interact with the SARS\u2010CoV\u20102 main target proteins, and the in vitro effects against cytokine\u2010induced\u2010inflammation and dysfunction in human umbilical vein endothelial cells (HUVECs). Computational analysis revealed that silibinin forms a stable complex with SARS\u2010CoV\u20102 spike protein RBD, has good negative binding affinity with Mpro, and interacts with many residues on the active site of Mpro, thus supporting its potentiality in inhibiting viral entry and replication. Moreover, HUVECs pretreatment with silibinin reduced TNF\u2010\u03b1\u2010induced gene expression of the proinflammatory genes IL\u20106 and MCP\u20101, as well as of PAI\u20101, a critical factor in coagulopathy and thrombosis, and of ET\u20101, a peptide involved in hemostatic vasoconstriction. Then, due to endothelium antiinflammatory and anticoagulant properties of silibinin and its capability to interact with SARS\u2010CoV\u20102 main target proteins demonstrated herein, silibinin could be a strong candidate for COVID\u201019 management from a multitarget perspective.<\/jats:p>","DOI":"10.1002\/ptr.7107","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T09:41:18Z","timestamp":1617702078000},"page":"4616-4625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Silibinin as potential tool against <scp>SARS\u2010Cov<\/scp>\u20102: In silico spike <scp>receptor\u2010binding<\/scp> domain and main protease molecular docking analysis, and in vitro endothelial protective effects"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-3892","authenticated-orcid":false,"given":"Antonio","family":"Speciale","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-1731","authenticated-orcid":false,"given":"Claudia","family":"Muscar\u00e0","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8841-589X","authenticated-orcid":false,"given":"Maria Sofia","family":"Molonia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-4797","authenticated-orcid":false,"given":"Francesco","family":"Cimino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-3596","authenticated-orcid":false,"given":"Antonella","family":"Saija","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-587X","authenticated-orcid":false,"given":"Salvatore Vincenzo","family":"Giofr\u00e8","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali Universit\u00e0 di Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.06.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05275-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.053"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830410202"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","unstructured":"Bayati A. 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