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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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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19ivm.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.
69 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N767, Dengue33,68,69, HIV-169, Simian virus 4070, Zika33,71,72, West Nile72, Yellow Fever73,74, Japanese encephalitis73, Chikungunya74, Semliki Forest virus74, Human papillomavirus53, Epstein-Barr53, BK Polyomavirus75, and Sindbis virus74.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins67,69,70,76, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing34, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination37,77, shows dose-dependent inhibition of wildtype and omicron variants32, exhibits dose-dependent inhibition of lung injury57,62, may inhibit SARS-CoV-2 via IMPase inhibition33, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation6, inhibits SARS-CoV-2 3CLpro50, may inhibit SARS-CoV-2 RdRp activity25, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages56, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation78, may interfere with SARS-CoV-2's immune evasion via ORF8 binding1, may inhibit SARS-CoV-2 by disrupting CD147 interaction79-82, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1955,83, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage5, may minimize SARS-CoV-2 induced cardiac damage36,44, increases Bifidobacteria which play a key role in the immune system84, has immunomodulatory47 and anti-inflammatory66,85 properties, and has an extensive and very positive safety profile86.
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 PaperIvermectinAll
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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