{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:44:54Z","timestamp":1771479894454,"version":"3.50.1"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100018533","name":"Major Scientific and Technological Special Project of Guizhou Province","doi-asserted-by":"publisher","award":["2023B1111050008"],"award-info":[{"award-number":["2023B1111050008"]}],"id":[{"id":"10.13039\/501100018533","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018540","name":"Science Fund for Distinguished Young Scholars of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515111165"],"award-info":[{"award-number":["2023A1515111165"]}],"id":[{"id":"10.13039\/501100018540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130101"],"award-info":[{"award-number":["82130101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017546","name":"Innovative Talent Fund of Harbin City","doi-asserted-by":"publisher","award":["2021B1111110003"],"award-info":[{"award-number":["2021B1111110003"]}],"id":[{"id":"10.13039\/501100017546","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M741601"],"award-info":[{"award-number":["2023M741601"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.phymed.2025.156989","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T14:44:20Z","timestamp":1750171460000},"page":"156989","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Dihydrotanshinone I targets the spike N-terminal domain to inhibit SARS-CoV-2 entry and spike-induced inflammation"],"prefix":"10.1016","volume":"145","author":[{"given":"Chan","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunyu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinshen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luping","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6638-6836","authenticated-orcid":false,"given":"Chunmei","family":"Nong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haobin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinhai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-5006","authenticated-orcid":false,"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2025.156989_bib0001","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41392-021-00851-6","article-title":"Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice","volume":"6","author":"Bi","year":"2021","journal-title":"Signal. Transduct. Target. Ther."},{"key":"10.1016\/j.phymed.2025.156989_bib0002","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1038\/s41591-024-03031-5","article-title":"Generating clinical evidence for treatment and prevention options for long COVID","volume":"30","author":"Buchholz","year":"2024","journal-title":"Nat. Med."},{"key":"10.1016\/j.phymed.2025.156989_bib0003","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104254","article-title":"Pharmacological activities of dihydrotanshinone I, a natural product from Salvia miltiorrhiza Bunge","volume":"145","author":"Chen","year":"2019","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2025.156989_bib0004","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.2174\/0929867328666210726094955","article-title":"Natural products with tandem anti-inflammatory, immunomodulatory and anti-SARS-CoV\/2 effects: a drug discovery perspective against SARS-CoV-2","volume":"29","author":"Da Cunha","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.phymed.2025.156989_bib0005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011805","article-title":"Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated golden Syrian hamsters","volume":"20","author":"Diego","year":"2024","journal-title":"PLoS. Pathog."},{"key":"10.1016\/j.phymed.2025.156989_bib0006","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.860383","article-title":"Salvia miltiorrhiza bunge (Danshen) and bioactive compound Tanshinone IIA alleviates cisplatin-induced acute kidney injury through regulating PXR\/NF-kappaB signaling","volume":"13","author":"Dou","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"4","key":"10.1016\/j.phymed.2025.156989_bib0007","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3390\/ph16040528","article-title":"Natural ingredients to improve immunity","volume":"16","author":"Gasmi","year":"2023","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.phymed.2025.156989_bib0008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010171","article-title":"Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells","volume":"18","author":"Grau-Exposito","year":"2022","journal-title":"PLoS. Pathog."},{"key":"10.1016\/j.phymed.2025.156989_bib0009","doi-asserted-by":"crossref","DOI":"10.1111\/all.15416","article-title":"Presentation of airway and general symptoms in Covid-19 caused by dominant SARS-CoV-2 variants: a follow-up on ARIA consensus","author":"Hagemann","year":"2022","journal-title":"Allergy"},{"key":"10.1016\/j.phymed.2025.156989_bib0010","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.phymed.2025.156989_bib0011","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41392-024-01847-8","article-title":"Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain","volume":"9","author":"Liu","year":"2024","journal-title":"Signal. Transduct. Target. Ther."},{"key":"10.1016\/j.phymed.2025.156989_bib0012","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.101895","article-title":"Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)","volume":"57","author":"Mastrorosa","year":"2023","journal-title":"EClinicalMedicine"},{"key":"10.1016\/j.phymed.2025.156989_bib0013","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.abn8652","article-title":"Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement","volume":"375","author":"Mccallum","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.phymed.2025.156989_bib0014","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1126\/science.abm8108","article-title":"The immunology and immunopathology of COVID-19","volume":"375","author":"Merad","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.phymed.2025.156989_bib0015","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1038\/s41467-020-18764-3","article-title":"SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate","volume":"11","author":"Olagnier","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phymed.2025.156989_bib0016","doi-asserted-by":"crossref","DOI":"10.1016\/j.virol.2024.110255","article-title":"Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization","volume":"600","author":"Oo","year":"2024","journal-title":"Virology"},{"key":"10.1016\/j.phymed.2025.156989_bib0017","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An oral SARS-CoV-2 M(pro) inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.phymed.2025.156989_bib0018","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.4049\/jimmunol.2400134","article-title":"Correction: selective inhibition of the interaction between SARS-CoV-2 spike S1 and ACE2 by SPIDAR peptide induces anti-inflammatory therapeutic responses","volume":"212","author":"Paidi","year":"2024","journal-title":"J. Immunol."},{"key":"10.1016\/j.phymed.2025.156989_bib0019","doi-asserted-by":"crossref","first-page":"5928","DOI":"10.1016\/j.bmc.2012.07.038","article-title":"Tanshinones as selective and slow-binding inhibitors for SARS-CoV cysteine proteases","volume":"20","author":"Park","year":"2012","journal-title":"Bioorgan. Med. Chem."},{"key":"10.1016\/j.phymed.2025.156989_bib0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.amsu.2022.104062","article-title":"Role of natural products towards the SARS-CoV-2: a critical review","volume":"80","author":"Raman","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"10.1016\/j.phymed.2025.156989_bib0021","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/s41467-024-45075-8","article-title":"Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue","volume":"15","author":"Shi","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phymed.2025.156989_bib0022","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.freeradbiomed.2022.01.015","article-title":"Dihydrotanshinone I inhibits ovarian tumor growth by activating oxidative stress through Keap1-mediated Nrf2 ubiquitination degradation","volume":"180","author":"Sun","year":"2022","journal-title":"Free Radic. Bio Med."},{"key":"10.1016\/j.phymed.2025.156989_bib0023","article-title":"Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial","volume":"111","author":"Viermyr","year":"2024","journal-title":"EBioMedicine"},{"key":"10.1016\/j.phymed.2025.156989_bib0024","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.joim.2022.08.001","article-title":"Potential medicinal plants involved in inhibiting 3CL(pro) activity: a practical alternate approach to combating COVID-19","volume":"20","author":"Yang","year":"2022","journal-title":"J. Integr. Med."},{"key":"10.1016\/j.phymed.2025.156989_bib0025","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s10753-021-01539-3","article-title":"Dihydrotanshinone attenuates LPS-induced acute lung injury in mice by upregulating LXRalpha","volume":"45","author":"Yue","year":"2022","journal-title":"Inflammation"},{"key":"10.1016\/j.phymed.2025.156989_bib0026","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.apsb.2020.09.006","article-title":"Activated PKB\/GSK-3beta synergizes with PKC-delta signaling in attenuating myocardial ischemia\/reperfusion injury via potentiation of NRF2 activity: therapeutic efficacy of dihydrotanshinone-I","volume":"11","author":"Zeng","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"issue":"1","key":"10.1016\/j.phymed.2025.156989_bib0027","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41392-021-00653-w","article-title":"Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct. Tar."},{"key":"10.1016\/j.phymed.2025.156989_bib0028","doi-asserted-by":"crossref","DOI":"10.1002\/mco2.70008","article-title":"Defining the features and structure of neutralizing antibody targeting the silent face of the SARS-CoV-2 spike N-terminal domain","volume":"5","author":"Zhang","year":"2024","journal-title":"MedComm"},{"key":"10.1016\/j.phymed.2025.156989_bib0029","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1002\/ptr.7580","article-title":"Promising natural products against SARS-CoV-2: structure, function, and clinical trials","volume":"36","author":"Zhao","year":"2022","journal-title":"PhytOther Res."},{"key":"10.1016\/j.phymed.2025.156989_bib0030","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s13238-021-00836-9","article-title":"High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors","volume":"12","author":"Zhao","year":"2021","journal-title":"Protein Cell."},{"key":"10.1016\/j.phymed.2025.156989_bib0031","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/s41422-021-00501-0","article-title":"Publisher correction: sARS-CoV-2 spike protein interacts with and activates TLR4","volume":"31","author":"Zhao","year":"2021","journal-title":"Cell Res."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325006282?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325006282?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T08:54:30Z","timestamp":1762332870000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711325006282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":31,"alternative-id":["S0944711325006282"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2025.156989","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dihydrotanshinone I targets the spike N-terminal domain to inhibit SARS-CoV-2 entry and spike-induced inflammation","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2025.156989","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier GmbH. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"156989"}}