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All Studies   Meta Analysis    Recent:   

1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein via inhibiting integrin αIIbβ3 outside‐in signaling

Wang et al., Cell Biochemistry and Function, doi:10.1002/cbf.4039
May 2024  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,500+ studies for 81 treatments. c19early.org
In Vitro study showing that calcitriol minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling. Authors find that calcitriol reduces platelet aggregation and Src-mediated signaling induced by the spike protein. Specifically, calcitriol attenuated spike protein-enhanced platelet spreading and the phosphorylation of β3, c-Src, and Syk. Using the Src family kinase inhibitor PP2, authors confirmed that the combination with calcitriol did not show additive inhibitory effects, suggesting that calcitriol operates through the same pathway.
21 preclinical studies support the efficacy of vitamin D for COVID-19:
Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function20-23. Vitamin D inhibits SARS-CoV-2 replication in vitro10,17, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections10,17, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression13, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells9, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway14, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects24, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling8, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1925. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity26,27.
Wang et al., 15 May 2024, peer-reviewed, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin DAll
{ 'indexed': {'date-parts': [[2024, 5, 17]], 'date-time': '2024-05-17T00:36:54Z', 'timestamp': 1715906214886}, 'reference-count': 36, 'publisher': 'Wiley', 'issue': '4', 'license': [ { 'start': { 'date-parts': [[2024, 5, 15]], 'date-time': '2024-05-15T00:00:00Z', 'timestamp': 1715731200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://onlinelibrary.wiley.com/termsAndConditions#vor'}], 'content-domain': { 'domain': ['analyticalsciencejournals.onlinelibrary.wiley.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2024, 6]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>Platelet hyperreactivity contributes to the ' 'pathogenesis of COVID‐19, which is associated with a hypercoagulability state and thrombosis ' 'disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity ' 'of COVID‐19 infection. Vitamin D supplement is widely used as a dietary supplement due to its ' 'safety and health benefits. In this study, we investigated the direct effects and underlying ' 'mechanisms of 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> on platelet ' 'hyperreactivity induced by SRAS‐CoV‐2 spike protein via Western blot and platelet functional ' 'studies in vitro. Firstly, we found that ' '1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> attenuated platelet aggregation and ' 'Src‐mediated signaling. We further observed that ' '1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> attenuated spike protein‐potentiated ' 'platelet aggregation in vitro. Mechanistically, ' '1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> attenuated spike protein ' 'upregulated‐integrin αIIbβ3 outside‐in signaling such as platelet spreading and the ' 'phosphorylation of β3, c‐Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to ' 'abolish spike protein‐stimulated platelet aggregation and integrin αIIbβ3 outside‐in ' 'signaling, the combination of PP2 and 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> ' 'did not show additive inhibitory effects on spike protein‐potentiated platelet aggregation ' 'and the phosphorylation of β3, c‐Src and Syk. Thus, our data suggest that ' '1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> attenuates platelet aggregation ' 'potentiated by spike protein via downregulating integrin αIIbβ3 outside‐in ' 'signaling.</jats:p>', 'DOI': '10.1002/cbf.4039', 'type': 'journal-article', 'created': {'date-parts': [[2024, 5, 16]], 'date-time': '2024-05-16T06:08:27Z', 'timestamp': 1715839707000}, 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': '1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein ' 'via inhibiting integrin αIIbβ3 outside‐in signaling', 'prefix': '10.1002', 'volume': '42', 'author': [ { 'given': 'Ruijie', 'family': 'Wang', 'sequence': 'first', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}, { 'name': 'Guangdong Engineering Technology Center of Nutrition ' 'Transformation Sun Yat‐sen University Shenzhen Guangdong ' 'Province China'}, { 'name': 'Guangdong Provincial Key Laboratory of Food, Nutrition and ' 'Health Sun Yat‐sen University Guangzhou Guangdong Province ' 'China'}]}, { 'given': 'Zezhong', 'family': 'Tian', 'sequence': 'additional', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}, { 'name': 'Guangdong Engineering Technology Center of Nutrition ' 'Transformation Sun Yat‐sen University Shenzhen Guangdong ' 'Province China'}, { 'name': 'Guangdong Provincial Key Laboratory of Food, Nutrition and ' 'Health Sun Yat‐sen University Guangzhou Guangdong Province ' 'China'}]}, { 'given': 'Caixia', 'family': 'Wang', 'sequence': 'additional', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}, { 'name': 'Guangdong Engineering Technology Center of Nutrition ' 'Transformation Sun Yat‐sen University Shenzhen Guangdong ' 'Province China'}, { 'name': 'Guangdong Provincial Key Laboratory of Food, Nutrition and ' 'Health Sun Yat‐sen University Guangzhou Guangdong Province ' 'China'}]}, { 'given': 'Bingying', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}]}, { 'given': 'Meiyan', 'family': 'Zhu', 'sequence': 'additional', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5662-4600', 'authenticated-orcid': False, 'given': 'Yan', 'family': 'Yang', 'sequence': 'additional', 'affiliation': [ { 'name': 'School of Public Health (Shenzhen) Shenzhen Campus of Sun ' 'Yat‐sen University Shenzhen Guangdong Province China'}, { 'name': 'Guangdong Engineering Technology Center of Nutrition ' 'Transformation Sun Yat‐sen University Shenzhen Guangdong ' 'Province China'}, { 'name': 'Guangdong Provincial Key Laboratory of Food, Nutrition and ' 'Health Sun Yat‐sen University Guangzhou Guangdong Province ' 'China'}]}], 'member': '311', 'published-online': {'date-parts': [[2024, 5, 15]]}, 'reference': [ { 'issue': '4', 'key': 'e_1_2_9_2_1', 'doi-asserted-by': 'crossref', 'first-page': '264', 'DOI': '10.1038/nri2956', 'article-title': 'Platelets and the immune continuum', 'volume': '11', 'author': 'Semple JW', 'year': '2011', 'journal-title': 'Nat Rev Immunol'}, { 'issue': '1', 'key': 'e_1_2_9_3_1', 'doi-asserted-by': 'crossref', 'first-page': '120', 'DOI': '10.1186/s13045-020-00954-7', 'article-title': 'SARS‐CoV‐2 binds platelet ACE2 to enhance thrombosis in COVID‐19', 'volume': '13', 'author': 'Zhang S', 'year': '2020', 'journal-title': 'J Hematol Oncol'}, { 'key': 'e_1_2_9_4_1', 'doi-asserted-by': 'crossref', 'DOI': '10.34133/research.0124', 'article-title': 'SARS‐CoV‐2 RBD and its variants can induce platelet activation and ' 'clearance: implications for antibody therapy and vaccinations against ' 'COVID‐19', 'volume': '6', 'author': 'Ma X', 'year': '2023', 'journal-title': 'Research'}, { 'issue': '7474', 'key': 'e_1_2_9_5_1', 'doi-asserted-by': 'crossref', 'first-page': '131', 'DOI': '10.1038/nature12613', 'article-title': 'A directional switch of integrin signalling and a new anti‐thrombotic ' 'strategy', 'volume': '503', 'author': 'Shen B', 'year': '2013', 'journal-title': 'Nature'}, { 'issue': '1', 'key': 'e_1_2_9_6_1', 'doi-asserted-by': 'crossref', 'first-page': '97', 'DOI': '10.1111/joim.13149', 'article-title': 'Perspective: vitamin D deficiency and COVID‐19 severity ‐ plausibly ' 'linked by latitude, ethnicity, impacts on cytokines, ACE2 and ' 'thrombosis', 'volume': '289', 'author': 'Rhodes JM', 'year': '2021', 'journal-title': 'J Intern Med'}, { 'issue': '9', 'key': 'e_1_2_9_7_1', 'doi-asserted-by': 'crossref', 'DOI': 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' 'and mortality', 'volume': '12', 'author': 'Gibbons JB', 'year': '2022', 'journal-title': 'Sci Rep'}], 'container-title': 'Cell Biochemistry and Function', 'original-title': [], 'language': 'en', 'deposited': { 'date-parts': [[2024, 5, 16]], 'date-time': '2024-05-16T06:08:38Z', 'timestamp': 1715839718000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/cbf.4039'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 5, 15]]}, 'references-count': 36, 'journal-issue': {'issue': '4', 'published-print': {'date-parts': [[2024, 6]]}}, 'alternative-id': ['10.1002/cbf.4039'], 'URL': 'http://dx.doi.org/10.1002/cbf.4039', 'relation': {}, 'ISSN': ['0263-6484', '1099-0844'], 'subject': [], 'container-title-short': 'Cell Biochemistry &amp;amp; Function', 'published': {'date-parts': [[2024, 5, 15]]}, 'assertion': [ { 'value': '2024-01-14', 'order': 0, 'name': 'received', 'label': 'Received', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2024-05-05', 'order': 1, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2024-05-15', 'order': 2, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
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