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All Studies   Meta Analysis    Recent:   

Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

Mok et al., bioRxiv, doi:10.1101/2020.06.21.162396
Jun 2020  
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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.
4,300+ studies for 75 treatments. c19early.org
In Vitro study showing that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2.
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.
Mok et al., 22 Jun 2020, preprint, 20 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin DAll
Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis
Chee Keng Mok, Yan Ling Ng, Bintou Ahmadou Ahidjo, Regina Ching Hua Lee, Marcus Wing Choy Loe, Jing Liu, Kai Sen Tan, Parveen Kaur, Wee Joo Chng, John Eu-Li Wong, De Yun Wang, Erwei Hao, Xiaotao Hou, Yong Wah Tan, Tze Minn Mak, Cui Lin, Raymond Lin, Paul Tambyah, Jiagang Deng, Justin Jang Hann Chu
doi:10.1101/2020.06.21.162396
, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.
Author contributions Conceived and designed the experiments: CKM, JJHC. Performed the experiments: CKM, YLN, BAA, RCHL. Analyzed the data: CKM, YLN, BAA, RCHL, MWCL, PK, PT, WJC, JEW, JJHC. Contributed reagents/materials: JL, KST, DYW, EH, XH JD, TMM, CL, RL. Wrote the paper: BAA, MWCL, YLN, RCHL, PK, CKM, YWT, JJHC. All the authors read the manuscript and approved it before submission
References
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Balicer, Huerta, Grotto, Tackling the next influenza pandemic, BMJ
Barnard, Hubbard, Burton, Smee, Morrey et al., Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-D-N4-hydroxycytidine, Antivir Chem Chemother
Dyall, Coleman, Hart, Venkataraman, Holbrook et al., Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection, Antimicrob Agents Chemother
Fajgenbaum, Khor, Gorzewski, Tamakloe, Powers et al., Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review, Infect Dis Ther
Freymuth, Vabret, Rozenberg, Dina, Petitjean et al., Replication of respiratory viruses, particularly influenza virus, rhinovirus, and coronavirus in HuH7 hepatocarcinoma cell line, J Med Virol
Gombart, The vitamin D-antimicrobial peptide pathway and its role in protection against infection, Future Microbiol
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res
Nair, Vitamin d deficiency and liver disease, Gastroenterology & hepatology
Nie, Wang, Shi, Wang, Chen et al., Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression, Biochem Biophys Res Commun
Rodriguez, Munoz-Castaneda, Almaden, Therapeutic use of calcitriol, Current vascular pharmacology
Sungnak, Huang, Becavin, Berg, Queen et al., SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Nat Med
Tu, Chien, Yarmishyn, Lin, Luo et al., A Review of SARS-CoV-2 and the Ongoing Clinical Trials, Int J Mol Sci
Van Genugten, Heijnen, Jager, Pandemic influenza and healthcare demand in the Netherlands: scenario analysis, Emerg Infect Dis
Wei, Li, Chiew, Yong, Toh et al., Presymptomatic Transmission of SARS-CoV-2 -Singapore, January 23, MMWR Morb Mortal Wkly Rep
Who, Rolling updates on coronavirus disease (COVID-19
Yan, Liu, Zhu, Huang, Dan et al., Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in hospitalised noncritically ill patients with SARS-CoV-2 infection, Eur Respir J
Yan, Tan, Li, Tran, Chao et al., Human nasal epithelial cells derived from multiple subjects exhibit differential responses to H3N2 influenza virus infection in vitro, J Allergy Clin Immunol
Zhao, Yu, Li, Li, Chao et al., The use of nasal epithelial stem/progenitor cells to produce functioning ciliated cells in vitro, Am J Rhinol Allergy
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
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