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Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors

Chellasamy et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277
Aug 2022  
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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 110 treatments. c19early.org
In Silico study of SARS-CoV-1&2 endodomains and ezrin docking, identifying ivermectin, quercetin, calcifediol, calcitriol, selamectin, and minocycline as potential therapeutic drugs with strong ezrin binding which may restrict viral endodomain interaction while also stabilizing ezrin, thereby reducing virus fusion and infection.
71 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,2,8,9,21,23,24,29,37,38,40,41,61-63, MproB,2,6,8,10,12,14,16,17,19,22,23,29,33,35-37,41,42,44,62-64, RNA-dependent RNA polymeraseC,2,8,31,63, PLproD,2,36,44, ACE2E,21,22,27,36,40,62, TMPRSS2F,21, nucleocapsidG,2, helicaseH,2,28,33, endoribonucleaseI,38, NSP16/10J,5, cathepsin LK,25, Wnt-3L,21, FZDM,21, LRP6N,21, ezrinO,39, ADRPP,37, NRP1Q,40, EP300R,15, PTGS2S,22, HSP90AA1T,15,22, matrix metalloproteinase 9U,30, IL-6V,20,34, IL-10W,20, VEGFAX,34, and RELAY,34 proteins. In Vitro studies demonstrate inhibition of the MproB,14,45,50,58 protein, and inhibition of spike-ACE2 interactionZ,46. In Vitro studies demonstrate efficacy in Calu-3AA,49, A549AB,20, HEK293-ACE2+AC,57, Huh-7AD,24, Caco-2AE,48, Vero E6AF,18,41,48, mTECAG,51, and RAW264.7AH,51 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAI,54, db/db miceAJ,51,60, BALB/c miceAK,59, and rats65. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice59, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages4, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity53.
Study covers quercetin, vitamin D, and ivermectin.
Chellasamy et al., 10 Aug 2022, peer-reviewed, 2 authors. Contact: selvaakumar.c@dypatil.edu, eleanorwatson@connect.glos.ac.uk.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors
Selvaa Kumar Chellasamy, Eleanor Watson
Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277
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.
Conflicts of Interest: The authors declare no competing or conflicting interests.
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