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Research Articles

Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study

, , , , , & ORCID Icon show all
Pages 11594-11610 | Received 01 Dec 2020, Accepted 22 Jul 2021, Published online: 20 Aug 2021

References

  • Alipio, M. (2020). Vitamin D supplementation could possibly improve clinical outcomes of patients infected with coronavirus-2019 (COVID-19). Available at SSRN 3571484.
  • Ardizzone, S., Cassinotti, A., Trabattoni, D., Manzionna, G., Rainone, V., Bevilacqua, M., Massari, A., Manes, G., Maconi, G., Clerici, M., & Bianchi Porro, G. (2009). Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on TH1/TH2 cytokines in inflammatory bowel disease: An in vitro study. International Journal of Immunopathology and Pharmacology, 22(1), 63–71. https://doi.org/10.1177/039463200902200108
  • Aygun, H. (2020). Vitamin D can prevent COVID-19 infection-induced multiple organ damage. Naunyn-Schmiedeberg's Archives of Pharmacology, 393(7), 1157–1160. https://doi.org/10.1007/s00210-020-01911-4
  • Bailey, N. T. J. (1995). Statistical methods in biology (Vol. third edition ed.). Cambridge University Press.
  • Baker, N. A., Sept, D., Joseph, S., Holst, M. J., & McCammon, J. A. (2001). Electrostatics of nanosystems: Application to microtubules and the ribosome. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10037–10041. https://doi.org/10.1073/pnas.181342398
  • Berendsen, H. J., & Hayward, S. (2000). Collective protein dynamics in relation to function. Current Opinion in Structural Biology, 10(2), 165–169. https://doi.org/10.1016/S0959-440X(00)00061-0
  • Bikle, D. D. (2008). Vitamin D receptor, UVR, and skin cancer: A potential protective mechanism. The Journal of Investigative Dermatology, 128(10), 2357–2361. https://doi.org/10.1038/jid.2008.249
  • Bikle, D. D. (2010a). Vitamin D and the skin. Journal of Bone and Mineral Metabolism, 28(2), 117–130. https://doi.org/10.1007/s00774-009-0153-8
  • Bikle, D. D. (2010b). Vitamin D: Newly discovered actions require reconsideration of physiologic requirements. Trends in Endocrinology and Metabolism: TEM, 21(6), 375–384. https://doi.org/10.1016/j.tem.2010.01.003
  • Bikle, D. D. (2011). Vitamin D metabolism and function in the skin. Molecular and Cellular Endocrinology, 347(1–2), 80–89. https://doi.org/10.1016/j.mce.2011.05.017
  • Bikle, D., & Christakos, S. (2020). New aspects of vitamin D metabolism and action – Addressing the skin as source and target. Nature Reviews Endocrinology, 16(4), 234–252. https://doi.org/10.1038/s41574-019-0312-5
  • Cantorna, M. T., & Mahon, B. D. (2005). D-hormone and the immune system. The Journal of Rheumatology. Supplement, 76, 11–20.
  • Case, D., Ben-Shalom, I., Brozell, S., Cerutti, D., Cheatham, T., III, Cruzeiro, V., Darden, T., Duke, R., Ghoreishi, D., & Gilson, M. (2018). AMBER 2018. University of California.
  • Chang, J. M., Di Tommaso, P., & Notredame, C. (2014). TCS: A new multiple sequence alignment reliability measure to estimate alignment accuracy and improve phylogenetic tree reconstruction. Molecular Biology and Evolution, 31(6), 1625–1637. https://doi.org/10.1093/molbev/msu117
  • Chang, J. M., Di Tommaso, P., Lefort, V., Gascuel, O., & Notredame, C. (2015). TCS: A web server for multiple sequence alignment evaluation and phylogenetic reconstruction. Nucleic Acids Research, 43(W1), W3–W6. https://doi.org/10.1093/nar/gkv310
  • Chen, J., Tang, Z., Slominski, A. T., Li, W., Żmijewski, M. A., Liu, Y., & Chen, J. (2020). Vitamin D and its analogs as anticancer and anti-inflammatory agents. European Journal of Medicinal Chemistry, 207, 112738. https://doi.org/10.1016/j.ejmech.2020.112738
  • Chen, J., Wang, J., Kim, T. K., Tieu, E. W., Tang, E. K., Lin, Z., Kovacic, D., Miller, D. D., Postlethwaite, A., Tuckey, R. C., Slominski, A. T., & Li, W. (2014). Novel vitamin D analogs as potential therapeutics: Metabolism, toxicity profiling, and antiproliferative activity. Anticancer Research, 34(5), 2153–2163.
  • Chen, Y., Zhang, J., Ge, X., Du, J., Deb, D. K., & Li, Y. C. (2013). Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein. The Journal of Biological Chemistry, 288(27), 19450–19458. https://doi.org/10.1074/jbc.M113.467670
  • Colovos, C., & Yeates, T. O. (1993). Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Science: A Publication of the Protein Society, 2(9), 1511–1519. https://doi.org/10.1002/pro.5560020916
  • Conti, P., Ronconi, G., Caraffa, A., Gallenga, C., Ross, R., Frydas, I., & Kritas, S. (2020). Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies. Journal of Biological Regulators and Homeostatic Agents, 34, 1.
  • Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. (2020). The species severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology, 5, 536–544.
  • D'Avolio, A., Avataneo, V., Manca, A., Cusato, J., De Nicolo, A., Lucchini, R., Keller, F., & Cantu, M. (2020). 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients, 12, 1359. https://doi.org/10.3390/nu12051359
  • Di Tommaso, P., Moretti, S., Xenarios, I., Orobitg, M., Montanyola, A., Chang, J. M., Taly, J. F., & Notredame, C. (2011). T-coffee: A web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension. Nucleic Acids Research, 39(Web Server issue), W13–W17. https://doi.org/10.1093/nar/gkr245
  • Dolinsky, T. J., Czodrowski, P., Li, H., Nielsen, J. E., Jensen, J. H., Klebe, G., & Baker, N. A. (2007). PDB2PQR: Expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Research, 35(Web Server issue), W522–W525. https://doi.org/10.1093/nar/gkm276
  • Dolinsky, T. J., Nielsen, J. E., McCammon, J. A., & Baker, N. A. (2004). PDB2PQR: An automated pipeline for the setup of Poisson–Boltzmann electrostatics calculations. Nucleic Acids Research, 32(Web Server issue), W665–W667. https://doi.org/10.1093/nar/gkh381
  • Dong, E., Du, H., & Gardner, L. (2020). An interactive web-based dashboard to track COVID-19 in real time. The Lancet. Infectious Diseases, 20(5), 533–534. https://doi.org/10.1016/S1473-3099(20)30120-1
  • Ebadi, M., & Montano-Loza, A. J. (2020). Perspective: Improving vitamin D status in the management of COVID-19. European Journal of Clinical Nutrition, 74(6), 856–859. https://doi.org/10.1038/s41430-020-0661-0
  • Efron, B., & Tibshirani, R. J. (1998). An introduction to the bootstrap. Chapman & Hall.
  • Entrenas Castillo, M., Entrenas Costa, L. M., Vaquero Barrios, J. M., Alcalá Díaz, J. F., López Miranda, J., Bouillon, R., & Quesada Gomez, J. M. (2020). Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of Steroid Biochemistry and Molecular Biology, 203, 105751. https://doi.org/10.1016/j.jsbmb.2020.105751
  • Ester, M., Kriegel, H.-P., Sander, J., & Xu, X. (1996). A density-based algorithm for discovering clusters in large spatial databases with noise. In Proceedings of 2nd International Conference on Knowledge Discovery and Data Mining (pp. 226–231).
  • Eswar, N., Webb, B., Marti-Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M. Y., Pieper, U., & Sali, A. (2006). Comparative protein structure modeling using Modeller. Curr Protoc Bioinformatics Chapter 5, Unit–5.6.
  • Ganoth, A., Friedman, R., Nachliel, E., & Gutman, M. (2006). A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides. Biophysical Journal, 91(7), 2436–2450. https://doi.org/10.1529/biophysj.106.085399
  • Grant, W. B., Lahore, H., McDonnell, S. L., Baggerly, C. A., French, C. B., Aliano, J. L., & Bhattoa, H. P. (2020). Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 12, 988. https://doi.org/10.3390/nu12123741
  • Gross, L. Z. F., Sacerdoti, M., Piiper, A., Zeuzem, S., Leroux, A. E., & Biondi, R. M. (2020). ACE2, the receptor that enables the infection by SARS‐CoV‐2: Biochemistry, structure, allostery and evaluation of the potential development of ACE2 modulators.
  • Hayward, S., Kitao, A., & Go, N. (1995). Harmonicity and anharmonicity in protein dynamics: A normal mode analysis and principal component analysis. Proteins, 23(2), 177–186. https://doi.org/10.1002/prot.340230207
  • Herter, S., Piper, D. E., Aaron, W., Gabriele, T., Cutler, G., Cao, P., Bhatt, A. S., Choe, Y., Craik, C. S., Walker, N., Meininger, D., Hoey, T., & Austin, R. J. (2005). Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. The Biochemical Journal, 390(Pt 1), 125–136. https://doi.org/10.1042/BJ20041955
  • Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Muller, M. A., Drosten, C., & Pohlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271–280.e28. https://doi.org/10.1016/j.cell.2020.02.052
  • Holick, M. F. (2003). Vitamin D: A millenium perspective. Journal of Cellular Biochemistry, 88(2), 296–307. https://doi.org/10.1002/jcb.10338
  • Holick, M. F. (2007). Vitamin D deficiency. The New England Journal of Medicine, 357(3), 266–281. https://doi.org/10.1056/NEJMra070553
  • Hooft, R. W., Vriend, G., Sander, C., & Abola, E. E. (1996). Errors in protein structures. Nature, 381(6580), 272. https://doi.org/10.1038/381272a0
  • Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
  • Jakovac, H. (2020). COVID-19 and vitamin D – Is there a link and an opportunity for intervention? American Journal of Physiology. Endocrinology and Metabolism, 318(5), E589. https://doi.org/10.1152/ajpendo.00138.2020
  • Janjetovic, Z., Tuckey, R. C., Nguyen, M. N., Thorpe, E. M., Jr., & Slominski, A. T. (2010). 23-Dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes. Journal of Cellular Physiology, 20, 36–48.
  • Janjetovic, Z., Zmijewski, M. A., Tuckey, R. C., DeLeon, D. A., Nguyen, M. N., Pfeffer, L. M., & Slominski, A. T. (2009). 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes. PLoS One, 4(6), e5988. https://doi.org/10.1371/journal.pone.0005988
  • Jenkinson, C. (2019). The vitamin D metabolome: An update on analysis and function. Cell Biochemistry and Function, 37(6), 408–423. https://doi.org/10.1002/cbf.3421
  • Jurrus, E., Engel, D., Star, K., Monson, K., Brandi, J., Felberg, L. E., Brookes, D. H., Wilson, L., Chen, J., Liles, K., Chun, M., Li, P., Gohara, D. W., Dolinsky, T., Konecny, R., Koes, D. R., Nielsen, J. E., Head-Gordon, T., Geng, W., … Baker, N. A. (2018). Improvements to the APBS biomolecular solvation software suite. Protein Science: A Publication of the Protein Society, 27(1), 112–128. https://doi.org/10.1002/pro.3280
  • Kabsch, W., & Sander, C. (1983). Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22(12), 2577–2637. https://doi.org/10.1002/bip.360221211
  • Kaufman, H. W., Niles, J. K., Kroll, M. H., Bi, C., & Holick, M. F. (2020). SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. Plos One, 15(9), e0239252. https://doi.org/10.1371/journal.pone.0239252
  • Kim, T. K., Atigadda, V., Brzeminski, P., Fabisiak, A., Tang, E. K. Y., Tuckey, R. C., & Slominski, A. T. (2020). Detection of 7-dehydrocholesterol and vitamin D3 derivatives in honey. Molecules, 25. https://doi.org/10.3390/molecules25112583
  • Kollman, P. A., Massova, I., Reyes, C., Kuhn, B., Huo, S., Chong, L., Lee, M., Lee, T., Duan, Y., Wang, W., Donini, O., Cieplak, P., Srinivasan, J., Case, D. A., & Cheatham, T. E. (2000). Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Accounts of Chemical Research, 33(12), 889–897. https://doi.org/10.1021/ar000033j
  • Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26(2), 283–291. https://doi.org/10.1107/S0021889892009944
  • Laskowski, R. A., Rullmannn, J. A., MacArthur, M. W., Kaptein, R., & Thornton, J. M. (1996). AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR. Journal of Biomolecular NMR, 8(4), 477–486. https://doi.org/10.1007/BF00228148
  • Lau, F. H., Majumder, R., Torabi, R., Saeg, F., Hoffman, R., Cirillo, J. D., & Greiffenstein, P. (2020). Vitamin D insufficiency is prevalent in severe COVID-19. medRxiv.
  • Lee, S. J., Song, Y., & Baker, N. A. (2008). Molecular dynamics simulations of asymmetric NaCl and KCl solutions separated by phosphatidylcholine bilayers: Potential drops and structural changes induced by strong Na+-lipid interactions and finite size effects. Biophysical Journal, 94(9), 3565–3576. https://doi.org/10.1529/biophysj.107.116335
  • Liu, Y., Pan, D., Bellis, S. L., & Song, Y. (2008). Effect of altered glycosylation on the structure of the I-like domain of beta1 integrin: A molecular dynamics study. Proteins, 73(4), 989–1000. https://doi.org/10.1002/prot.22126
  • MATLAB. (2015). (R2015a). The MathWorks Inc.
  • Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet (London, England), 395(10229), 1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0
  • Meltzer, D. O., Best, T. J., Zhang, H., Vokes, T., Arora, V., & Solway, J. (2020). Association of Vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Network Open, 3(9), e2019722. https://doi.org/10.1001/jamanetworkopen.2020.19722
  • Meng, T., Cao, H., Zhang, H., Kang, Z., Xu, D., Gong, H., Wang, J., Li, Z., Cui, X., Xu, H., Wei, H., Pan, X., Zhu, R., Xiao, J., Zhou, W., Cheng, L., & Liu, J. (2020). The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS. bioRxiv. 2020.2002.2008.926006.
  • Merzon, E., Tworowski, D., Gorohovski, A., Vinker, S., Golan Cohen, A., Green, I., & Frenkel-Morgenstern, M. (2020). Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: An Israeli population-based study. The FEBS Journal, 287(17), 3693–3702. https://doi.org/10.1111/febs.15495
  • Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
  • Muralidharan Jothimani, M. P., Al-Sehemi, A. G., & Muthusamy, K. (2021). Association of vitamin-D and VDR with ACE2 modulates the severity in COVID-19. EC Orthopaedics, 12, 87–92.
  • Notredame, C., Higgins, D. G., & Heringa, J. (2000). T-coffee: A novel method for fast and accurate multiple sequence alignment. Journal of Molecular Biology, 302(1), 205–217. https://doi.org/10.1006/jmbi.2000.4042
  • Pan, D., & Song, Y. (2010). Role of altered sialylation of the I-like domain of beta1 integrin in the binding of fibronectin to beta1 integrin: Thermodynamics and conformational analyses. Biophysical Journal, 99(1), 208–217. https://doi.org/10.1016/j.bpj.2010.03.063
  • Pan, D., Yan, Q., Chen, Y., McDonald, J. M., & Song, Y. (2011). Trifluoperazine regulation of calmodulin binding to Fas: A computational study. Proteins, 79(8), 2543–2556. https://doi.org/10.1002/prot.23081
  • Perrotta, F., Matera, M. G., Cazzola, M., & Bianco, A. (2020). Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Respiratory Medicine, 168, 105996. https://doi.org/10.1016/j.rmed.2020.105996
  • Plum, L. A., & DeLuca, H. F. (2010). Vitamin D, disease and therapeutic opportunities. Nature Reviews. Drug Discovery, 9(12), 941–955. https://doi.org/10.1038/nrd3318
  • Provvedini, D. M., Tsoukas, C. D., Deftos, L. J., & Manolagas, S. C. (1983). 1,25-Dihydroxyvitamin D3 receptors in human leukocytes. Science (New York, N.Y.), 221(4616), 1181–1183. https://doi.org/10.1126/science.6310748
  • PyMOL. (2020). The PyMOL Molecular Graphics System v. 2.4.0. Schrödinger, LLC. https://pymol.org/2/.
  • Quesada-Gomez, J. M., Entrenas-Castillo, M., & Bouillon, R. (2020). Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. The Journal of Steroid Biochemistry and Molecular Biology, 202, 105719. https://doi.org/10.1016/j.jsbmb.2020.105719
  • Rhodes, J. M., Subramanian, S., Laird, E., Griffin, G., & Kenny, R. A. (2021). Perspective: Vitamin D deficiency and COVID-19 severity – Plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis (R1). Journal of Internal Medicine, 289(1), 97–115. https://doi.org/10.1111/joim.13149
  • Samuel, S., & Sitrin, M. D. (2008). Vitamin D's role in cell proliferation and differentiation. Nutrition Reviews, 66(10 Suppl 2), S116–S124. https://doi.org/10.1111/j.1753-4887.2008.00094.x
  • Schleithoff, S. S., Zittermann, A., Tenderich, G., Berthold, H. K., Stehle, P., & Koerfer, R. (2006). Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. The American Journal of Clinical Nutrition, 83(4), 754–759. https://doi.org/10.1093/ajcn/83.4.754
  • Schrödinger. (2021). (2021-1) Maestro 12.4. Schrödinger, LLC.
  • Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., & Li, F. (2020). Cell entry mechanisms of SARS-CoV-2. Proceedings of the National Academy of Sciences of the United States of America, 117(21), 11727–11734. https://doi.org/10.1073/pnas.2003138117
  • Slominski, A. T., Chaiprasongsuk, A., Janjetovic, Z., Kim, T. K., Stefan, J., Slominski, R. M., Hanumanthu, V. S., Raman, C., Qayyum, S., Song, Y., Song, Y., Panich, U., Crossman, D. K., Athar, M., Holick, M. F., Jetten, A. M., Zmijewski, M. A., Zmijewski, J., & Tuckey, R. C. (2020a). Photoprotective properties of vitamin D and lumisterol hydroxyderivatives. Cell Biochemistry and Biophysics, 78(2), 165–180. https://doi.org/10.1007/s12013-020-00913-6
  • Slominski, A. T., Janjetovic, Z., Fuller, B. E., Zmijewski, M. A., Tuckey, R. C., Nguyen, M. N., Sweatman, T., Li, W., Zjawiony, J., Miller, D., Chen, T. C., Lozanski, G., & Holick, M. F. (2010). Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One, 5(3), e9907. https://doi.org/10.1371/journal.pone.0009907
  • Slominski, A. T., Kim, T. K., Hobrath, J. V., Oak, A. S. W., Tang, E. K. Y., Tieu, E. W., Li, W., Tuckey, R. C., & Jetten, A. M. (2017). Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased" agonists on VDR and inverse agonists on RORα and RORγ. The Journal of Steroid Biochemistry and Molecular Biology, 173, 42–56. https://doi.org/10.1016/j.jsbmb.2016.09.024
  • Slominski, A. T., Kim, T. K., Janjetovic, Z., Brozyna, A. A., Zmijewski, M. A., Xu, H., Sutter, T. R., Tuckey, R. C., Jetten, A. M., & Crossman, D. K. (2018). Differential and overlapping effects of 20,23(OH)(2)D3 and 1,25(OH)(2)D3 on gene expression in human epidermal keratinocytes: Identification of AhR as an alternative receptor for 20,23(OH)(2)D3. International Journal of Molecular Sciences, 19, 23.
  • Slominski, A. T., Kim, T. K., Li, W., Postlethwaite, A., Tieu, E. W., Tang, E. K., & Tuckey, R. C. (2015). Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. Scientific Reports, 5, 14875. https://doi.org/10.1038/srep14875
  • Slominski, A. T., Kim, T. K., Li, W., Yi, A. K., Postlethwaite, A., & Tuckey, R. C. (2014a). The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions. The Journal of Steroid Biochemistry and Molecular Biology, 144 Pt A, 28–39. https://doi.org/10.1016/j.jsbmb.2013.10.012
  • Slominski, A. T., Kim, T. K., Shehabi, H. Z., Semak, I., Tang, E. K., Nguyen, M. N., Benson, H. A., Korik, E., Janjetovic, Z., Chen, J., Yates, C. R., Postlethwaite, A., Li, W., & Tuckey, R. C. (2012). In vivo evidence for a novel pathway of vitamin D₃ metabolism initiated by P450scc and modified by CYP27B1. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 26(9), 3901–3915. https://doi.org/10.1096/fj.12-208975
  • Slominski, A. T., Kim, T. K., Takeda, Y., Janjetovic, Z., Brozyna, A. A., Skobowiat, C., Wang, J., Postlethwaite, A., Li, W., Tuckey, R. C., & Jetten, A. M. (2014b). RORα and ROR γ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 28(7), 2775–2789. https://doi.org/10.1096/fj.13-242040
  • Slominski, A. T., Kim, T.-K., Qayyum, S., Song, Y., Janjetovic, Z., Oak, A. S. W., Slominski, R. M., Raman, C., Stefan, J., Mier-Aguilar, C. A., Atigadda, V., Crossman, D. K., Golub, A., Bilokin, Y., Tang, E. K. Y., Chen, J. Y., Tuckey, R. C., Jetten, A. M., & Song, Y. (2021). Vitamin D and lumisterol derivatives can act on liver X receptors (LXRs). Scientific Reports, 11(1), 8002. https://doi.org/10.1038/s41598-021-87061-w
  • Slominski, A. T., Slominski, R. M., Goepfert, P. A., Kim, T. K., Holick, M. F., Jetten, A. M., & Raman, C. (2020b). Reply to Jakovac and to Rocha et al.: Can vitamin D prevent or manage COVID-19 illness? American Journal of Physiology. Endocrinology and Metabolism, 319(2), E455–E457. https://doi.org/10.1152/ajpendo.00348.2020
  • Slominski, A., Janjetovic, Z., Tuckey, R. C., Nguyen, M. N., Bhattacharya, K. G., Wang, J., Li, W., Jiao, Y., Gu, W., Brown, M., & Postlethwaite, A. E. (2013). 20S-hydroxyvitamin D3, noncalcemic product of CYP11A1 action on vitamin D3, exhibits potent antifibrogenic activity in vivo. The Journal of clinical endocrinology and metabolism, 98(2), E298–E303. https://doi.org/10.1210/jc.2012-3074
  • Slominski, R. M., Stefan, J., Athar, M., Holick, M. F., Jetten, A. M., Raman, C., & Slominski, A. T. (2020c). COVID-19 and Vitamin D: A lesson from the skin. Experimental Dermatology, 29(9).
  • Slominski, R. M., Tuckey, R. C., Manna, P. R., Jetten, A. M., Postlethwaite, A., Raman, C., & Slominski, A. T. (2020d). Extra-adrenal glucocorticoid biosynthesis: Implications for autoimmune and inflammatory disorders. Genes and Immunity, 21(3), 150–168. https://doi.org/10.1038/s41435-020-0096-6
  • Song, Y., Guallar, V., & Baker, N. A. (2005). Molecular dynamics simulations of salicylate effects on the micro- and mesoscopic properties of a dipalmitoylphosphatidylcholine bilayer. Biochemistry, 44(41), 13425–13438. https://doi.org/10.1021/bi0506829
  • Suever, J. D., Chen, Y., McDonald, J. M., & Song, Y. (2008). Conformation and free energy analyses of the complex of calcium-bound calmodulin and the Fas death domain. Biophysical Journal, 95(12), 5913–5921. https://doi.org/10.1529/biophysj.108.130542
  • Sun, D., Luo, F., Xing, J.-C., Zhang, F., Xu, J-z., & Zhang, Z-h. (2018). 1,25(OH)2 D3 inhibited Th17 cells differentiation via regulating the NF-κB activity and expression of IL-17. Cell Proliferation, 51(5), e12461. https://doi.org/10.1111/cpr.12461
  • Sung, B., Ravindran, J., Prasad, S., Pandey, M. K., & Aggarwal, B. B. (2010). Gossypol induces death receptor-5 through activation of the ROS-ERK-CHOP pathway and sensitizes colon cancer cells to TRAIL. The Journal of Biological Chemistry, 285(46), 35418–35427. https://doi.org/10.1074/jbc.M110.172767
  • Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
  • Tsoukas, C. D., Provvedini, D. M., & Manolagas, S. C. (1984). 1,25-Dihydroxyvitamin D3: A novel immunoregulatory hormone. Science (New York, N.Y.), 224(4656), 1438–1440. https://doi.org/10.1126/science.6427926
  • Tuckey, R. C., Cheng, C. Y. S., & Slominski, A. T. (2019). The serum vitamin D metabolome: What we know and what is still to discover. The Journal of Steroid Biochemistry and Molecular Biology, 186, 4–21. https://doi.org/10.1016/j.jsbmb.2018.09.003
  • Wang, J., Slominski, A., Tuckey, R. C., Janjetovic, Z., Kulkarni, A., Chen, J., Postlethwaite, A. E., Miller, D., & Li, W. (2012). 20-hydroxyvitamin D(3) inhibits proliferation of cancer cells with high efficacy while being non-toxic. Anticancer Research, 32(3), 739–746.
  • Wang, J., Wang, W., Kollman, P. A., & Case, D. A. (2001). Antechamber: An accessory software package for molecular mechanical calculations. Journal of the American Chemical Society, 222, U403.
  • Wang, L., Murphy-Ullrich, J. E., & Song, Y. (2014). Molecular insight into the effect of lipid bilayer environments on thrombospondin-1 and calreticulin interactions. Biochemistry, 53(40), 6309–6322. https://doi.org/10.1021/bi500662v
  • Wang, L., Murphy-Ullrich, J. E., & Song, Y. (2019). Multiscale simulation of the interaction of calreticulin–thrombospondin-1 complex with a model membrane microdomain. Journal of Biomolecular Structure & Dynamics, 37(3), 811–822. https://doi.org/10.1080/07391102.2018.1433065
  • Wang, L., Pan, D., Yan, Q., & Song, Y. (2017). Activation mechanisms of αVβ3 integrin by binding to fibronectin: A computational study. Protein Science: A Publication of the Protein Society, 26(6), 1124–1137. https://doi.org/10.1002/pro.3163
  • Wang, W., Lim, W. A., Jakalian, A., Wang, J., Wang, J., Luo, R., Bayly, C. I., & Kollman, P. A. (2001). An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations, and sequence analysis. Journal of the American Chemical Society, 123(17), 3986–3994. https://doi.org/10.1021/ja003164o
  • Wilson, S., Greer, B., Hooper, J., Zijlstra, A., Walker, B., Quigley, J., & Hawthorne, S. (2005). The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. The Biochemical Journal, 388(Pt 3), 967–972. https://doi.org/10.1042/BJ20041066
  • Yan, Q., Murphy-Ullrich, J. E., & Song, Y. H. (2010). Structural insight into the role of thrombospondin-1 binding to calreticulin in calreticulin-induced focal adhesion disassembly. Biochemistry, 49(17), 3685–3694. https://doi.org/10.1021/bi902067f
  • Yan, Q., Murphy-Ullrich, J. E., & Song, Y. H. (2011). Molecular and structural insight into the role of key residues of thrombospondin-1 and calreticulin in thrombospondin-1–calreticulin binding. Biochemistry, 50(4), 566–573. https://doi.org/10.1021/bi101639y
  • Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., & Zhou, Q. (2020). Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science (New York, N.Y.), 367(6485), 1444–1448. https://doi.org/10.1126/science.abb2762
  • Yang, H., & Song, Y. (2016). Structural insight for roles of DR5 death domain mutations on oligomerization of DR5 death domain-FADD complex in the death-inducing signaling complex formation: A computational study. Journal of Molecular Modeling, 22(4), 89. https://doi.org/10.1007/s00894-016-2941-0
  • Zhang, R., Wang, X., Ni, L., Di, X., Ma, B., Niu, S., Liu, C., & Reiter, R. J. (2020a). COVID-19: Melatonin as a potential adjuvant treatment. Life Sciences, 250, 117583. https://doi.org/10.1016/j.lfs.2020.117583
  • Zhang, Y., Xiao, M., Zhang, S., Xia, P., Cao, W., Jiang, W., Chen, H., Ding, X., Zhao, H., Zhang, H., Wang, C., Zhao, J., Sun, X., Tian, R., Wu, W., Wu, D., Ma, J., Chen, Y., Zhang, D., … Zhang, S. (2020b). Coagulopathy and antiphospholipid antibodies in patients with Covid-19. The New England Journal of Medicine, 382(17), e38. https://doi.org/10.1056/NEJMc2007575
  • Zmijewski, M. A., & Carlberg, C. (2020). Vitamin D receptor(s): In the nucleus but also at membranes? Experimental Dermatology, 29(9), 876–884. https://doi.org/10.1111/exd.14147

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