{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:35:45Z","timestamp":1785159345366,"version":"3.55.0"},"reference-count":117,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VA merit","award":["1I01BX004293-01A1"],"award-info":[{"award-number":["1I01BX004293-01A1"]}]},{"name":"VA merit","award":["1R01AR073004"],"award-info":[{"award-number":["1R01AR073004"]}]},{"name":"VA merit","award":["R01AR071189"],"award-info":[{"award-number":["R01AR071189"]}]},{"name":"VA merit","award":["R21AI149267-01A1"],"award-info":[{"award-number":["R21AI149267-01A1"]}]},{"name":"NIH","award":["1I01BX004293-01A1"],"award-info":[{"award-number":["1I01BX004293-01A1"]}]},{"name":"NIH","award":["1R01AR073004"],"award-info":[{"award-number":["1R01AR073004"]}]},{"name":"NIH","award":["R01AR071189"],"award-info":[{"award-number":["R01AR071189"]}]},{"name":"NIH","award":["R21AI149267-01A1"],"award-info":[{"award-number":["R21AI149267-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin D deficiency is associated with a higher risk of SARS-CoV-2 infection and poor outcomes of the COVID-19 disease. However, a satisfactory mechanism explaining the vitamin D protective effects is missing. Based on the anti-inflammatory and anti-oxidative properties of classical and novel (CYP11A1-derived) vitamin D and lumisterol hydroxymetabolites, we have proposed that they would attenuate the self-amplifying damage in lungs and other organs through mechanisms initiated by interactions with corresponding nuclear receptors. These include the VDR mediated inhibition of NF\u03ba\u03b2, inverse agonism on ROR\u03b3 and the inhibition of ROS through activation of NRF2-dependent pathways. In addition, the non-receptor mediated actions of vitamin D and related lumisterol hydroxymetabolites would include interactions with the active sites of SARS-CoV-2 transcription machinery enzymes (Mpro;main protease and RdRp;RNA dependent RNA polymerase). Furthermore, these metabolites could interfere with the binding of SARS-CoV-2 RBD with ACE2 by interacting with ACE2 and TMPRSS2. These interactions can cause the conformational and dynamical motion changes in TMPRSS2, which would affect TMPRSS2 to prime SARS-CoV-2 spike proteins. Therefore, novel, CYP11A1-derived, active forms of vitamin D and lumisterol can restrain COVID-19 through both nuclear receptor-dependent and independent mechanisms, which identify them as excellent candidates for antiviral drug research and for the educated use of their precursors as nutrients or supplements in the prevention and attenuation of the COVID-19 disease.<\/jats:p>","DOI":"10.3390\/nu14224779","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:21:45Z","timestamp":1668399705000},"page":"4779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-1994","authenticated-orcid":false,"given":"Shariq","family":"Qayyum","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Research Program in Men\u2019s Health: Aging and Metabolism, The Center for Clinical Investigation, Brigham and Women\u2019s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radomir M.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Genetics, Informatics Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chander","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8963-3995","authenticated-orcid":false,"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Pathology and Laboratory Medicine Service, VA Medical Center, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). 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