{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:56:26Z","timestamp":1784728586678,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The severe acute respiratory syndrome coronavirus (SARS\u2010CoV\u20102) pandemic has triggered a significant impact on global public health security, it is urgent to develop effective antiviral drugs. Previous studies have found that binding to ACE2 is a key step in the invasion of SARS\u2010CoV\u20102 into host cells, so virus invasion can be inhibited by blocking ACE2, but there are few reports on this kind of specific inhibitor. Our previous study found that Harringtonine (HT) can inhibit the entry of SARS\u2010CoV\u20102 spike pseudovirus into ACE2<jats:sup>h<\/jats:sup> cells, but its relatively high cytotoxicity limits its further development. Amino acid modification of the active components can increase their solubility and reduce their cytotoxicity. Therefore, in this study, seven new derivatives were synthesized by amino acid modification of its core structure Cephalotaxine. The target compounds were evaluated by cell viability assay and the SARS\u2010CoV\u20102 spike pseudovirus entry assay. Compound CET\u20101 significantly inhibited the entry of pseudovirus into ACE2<jats:sup>h<\/jats:sup> cells and showed less cytotoxicity than HT. Molecular docking results showed that CET\u20101 could bind TYR83, an important residue of ACE2, just like HT. In conclusion, our study provided a novel compound with more potential activity and lower toxicity than HT on inhibiting the SARS\u2010CoV\u20102 spike pseudovirus infection, which makes it possible to be a lead compound as an antiviral drug in the future.<\/jats:p>","DOI":"10.1111\/cbdd.14566","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T01:49:32Z","timestamp":1718070572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and anti\u2010<scp>SARS<\/scp>\u2010<scp>CoV<\/scp>\u20102 activity of amino acid modified cephalotaxine derivatives"],"prefix":"10.1111","volume":"103","author":[{"given":"Min","family":"Si","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meidi","family":"An","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaomin","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Mo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2836-2308","authenticated-orcid":false,"given":"Huaizhen","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9298"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.06.046"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.09.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2014.02.102"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115617"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107843"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010021\u201000418\u2010x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10126\u2010017\u20109785\u20101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01467\u201012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275\u2010019\u20108514\u2010z"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25184082"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2021.09.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphar.2021.100055"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102179\u2010y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2021.12.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28312"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.789180"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytol.2018.09.007"},{"key":"e_1_2_9_22_1","unstructured":"World Health Organization (WHO). (2023).Weekly epidemiological update on COVID\u201019.https:\/\/covid19.who.int\/"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T12:03:07Z","timestamp":1719489787000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/cbdd.14566"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14566","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2023-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14566"}}