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Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes

Qayyum et al., Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021
Jul 2021  
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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.
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4,400+ studies for 79 treatments.
In Silico analysis showing that vitamin D and lumisterol metabolites may inhibit SARS-CoV-2 Mpro and RdRP.
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.
Qayyum et al., 27 Jul 2021, peer-reviewed, 7 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin DAll
Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes
Shariq Qayyum, Taj Mohammad, Radomir M Slominski, Md Imtaiyaz Hassan, Robert C Tuckey, Chander Raman, Andrzej T Slominski
American Journal of Physiology-Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021
Vitamin D deficiency significantly correlates with the severity of SARS-CoV-2 infection. Molecular docking-based virtual screening studies predict that novel vitamin D and related lumisterol hydroxymetabolites are able to bind to the active sites of two SARS-CoV-2 transcription machinery enzymes with high affinity. These enzymes are the main protease (M pro ) and RNA-dependent RNA polymerase (RdRP), which play important roles in viral replication and establishing infection. Based on predicted binding affinities and specific interactions, we identified 10 vitamin D3 (D3) and lumisterol (L3) analogs as likely binding partners of SARS-CoV-2 M pro and RdRP and, therefore, tested their ability to inhibit these enzymes. Activity measurements demonstrated that 25 (OH)L3, 24(OH)L3, and 20(OH)7DHC are the most effective of the hydroxymetabolites tested at inhibiting the activity of SARS-CoV-2 M pro causing 10%-19% inhibition. These same derivatives as well as other hydroxylumisterols and hydroxyvitamin D3 metabolites inhibited RdRP by 50%-60%. Thus, inhibition of these enzymes by vitamin D and lumisterol metabolites may provide a novel approach to hindering the SARS-CoV-2 infection. NEW & NOTEWORTHY Active forms of vitamin D and lumisterol can inhibit SARS-CoV-2 replication machinery enzymes, which indicates that novel vitamin D and lumisterol metabolites are candidates for antiviral drug research.
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