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The spike protein of SARS-CoV-2 virus induces heme oxygenase-1: Pathophysiologic implications

Singh et al., Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, doi:10.1016/j.bbadis.2021.166322
Dec 2021  
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Quercetin for COVID-19
24th treatment shown to reduce risk in July 2021, now with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
In Vitro study transfecting SARS-CoV-2 viral spike protein in kidney cell lines, showing syncytia formation and upregulation of the cytoprotective gene HO-1, and that quercetin, which induces HO-1, can reduce syncytia formation. Authors conclude that quercetin may be protective for AKI in COVID-19.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
68 preclinical studies support the efficacy of quercetin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,6,7,19,21,22,27,35,36,38,39,59,60, MproB,4,6,8,10,12,14,15,17,20,21,27,31,33-35,39,40,42,60,61, RNA-dependent RNA polymeraseC,6,29, PLproD,34,42, ACE2E,19,20,25,34,38,60, TMPRSS2F,19, helicaseG,26,31, endoribonucleaseH,36, NSP16/10I,3, cathepsin LJ,23, Wnt-3K,19, FZDL,19, LRP6M,19, ezrinN,37, ADRPO,35, NRP1P,38, EP300Q,13, PTGS2R,20, HSP90AA1S,13,20, matrix metalloproteinase 9T,28, IL-6U,18,32, IL-10V,18, VEGFAW,32, and RELAX,32 proteins. In Vitro studies demonstrate inhibition of the MproB,12,43,48,56 protein, and inhibition of spike-ACE2 interactionY,44. In Vitro studies demonstrate efficacy in Calu-3Z,47, A549AA,18, HEK293-ACE2+AB,55, Huh-7AC,22, Caco-2AD,46, Vero E6AE,16,39,46, mTECAF,49, and RAW264.7AG,49 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAH,52, db/db miceAI,49,58, BALB/c miceAJ,57, and rats62. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice57, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages2, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity51.
Singh et al., 14 Dec 2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications
Ph.D Raman Deep Singh, Ph.D Michael A Barry, Anthony J Croatt, M.S Allan W Ackerman, M.D Joseph P Grande, Ph.D Rosa M Diaz, Ph.D Richard G Vile, M.D Anupam Agarwal, MB. ChB Karl A Nath
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, doi:10.1016/j.bbadis.2021.166322
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Authors' contributions Raman Deep Singh: Conceptualisation, data curation, formal analysis, investigation, methodology, project administration, resources, software, validation, visualisation, writingoriginal draft, and writingreview & editing. Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J o u r n a l P r e -p r o o f
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