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All Studies   Meta Analysis       

Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2

Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134
Jun 2020  
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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 110 treatments. c19ivm.org
In silico analysis showing ivermectin may interfere with the attachment of the spike to the human cell membrane.
70 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 H7N768, Dengue34,69,70, HIV-170, Simian virus 4071, Zika34,72,73, West Nile73, Yellow Fever74,75, Japanese encephalitis74, Chikungunya75, Semliki Forest virus75, Human papillomavirus54, Epstein-Barr54, BK Polyomavirus76, and Sindbis virus75.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins68,70,71,77, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing35, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination38,78, shows dose-dependent inhibition of wildtype and omicron variants33, exhibits dose-dependent inhibition of lung injury58,63, may inhibit SARS-CoV-2 via IMPase inhibition34, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation7, inhibits SARS-CoV-2 3CLpro51, may inhibit SARS-CoV-2 RdRp activity26, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages57, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation79, may interfere with SARS-CoV-2's immune evasion via ORF8 binding2, may inhibit SARS-CoV-2 by disrupting CD147 interaction80-83, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1956,84, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage6, may minimize SARS-CoV-2 induced cardiac damage37,45, increases Bifidobacteria which play a key role in the immune system85, has immunomodulatory48 and anti-inflammatory67,86 properties, and has an extensive and very positive safety profile87.
Lehrer et al., 19 Jun 2020, peer-reviewed, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Common drugs, vitamins, nutritional supplements and COVID-19 mortality
Dr Steven Lehrer, Peter H Rheinstein
doi:10.3892/ijfn.2021.14
The FDA has approved only one drug, remdesivir, for the treatment of COVID-19. The FDA has granted an emergency use authorization for the rheumatoid arthritis treatment drug, baricitinib (Olumiant), for the treatment of COVID-19 in some cases. For this reason, investigators have paid considerable attention to the association between commonly used drugs and the outcome of patients with COVID-19. Aspirin and ibuprofen have been reported to reduce the mortality rate. Omeprazole can increase mortality. In addition, some studies have demonstrated that famotidine diminishes mortality, while others have indicated that famotidine leads to a poorer prognosis. The present study used UK Biobank (UKB) data to assess the association of commonly used drugs with COVID-19 mortality. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6. The UK Biobank Data Parser (ukbb_parser) was used, a python-based package that allows easy interfacing with the large UK Biobank dataset. The results revealed that aspirin and omeprazole were associated with an elevated mortality rate. Ibuprofen-related mortality was lower than laxative-related mortality. Aspirin users were also significantly older than other subjects. The association with mortality of cholesterol-lowering medications, blood pressure-lowering medications, hormone replacement and oral contraceptives in 134 female subjects revealed insignificant variability. The association of nutritional supplements in 238 subjects with mortality indicated that variability was insignificant. The lower mortality linked to the supplementation of vitamin D and vitamin B, presumably B complex, has been previously observed. On the whole, the present study demonstrates that although some of the associations described among drugs and This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
Ethics approval and consent to participate All patient data were from the UK Biobank. The UK Biobank application for the present study was approved as UKB project 57245, SL and PHR. Patient consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author Manuscript The research reported in the present study was supported by the Office of Research Infrastructure of the National Institutes of Health under award nos. S10OD018522 and S10OD026880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author Manuscript
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Pavoni, Gianesello, Pazzi, Stera, Meconi et al., Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action, Thromb Res
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Yuan, Wang, Chan, Zhang, Cheng et al., Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virusassociated pneumonia in Syrian hamsters, Nat Microbiol
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