Quantitative proteomics of Ivermectin's antiviral properties identify antiviral (CMV, HPV, EBV & HIV) pathways w/ COVID overlap. Can it apply to CFS?

junkcrap50

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536980/
Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment
Na Li, 1 , 2 , 3 Lingfeng Zhao, 4 and Xianquan Zhan
1 , 2 , 3 , 5 , 6
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Abstract
Viruses such as human cytomegalovirus (HCMV), human papillomavirus (HPV), Epstein–Barr virus (EBV), human immunodeficiency virus (HIV), and coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) represent a great burden to human health worldwide. FDA‐approved anti‐parasite drug ivermectin is also an antibacterial, antiviral, and anticancer agent, which offers more potentiality to improve global public health, and it can effectively inhibit the replication of SARS‐CoV‐2 in vitro. This study sought to identify ivermectin‐related virus infection pathway alterations in human ovarian cancer cells. Stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics was used to analyze human ovarian cancer cells TOV‐21G treated with and without ivermectin (20 μmol/L) for 24 h, which identified 4447 ivermectin‐related proteins in ovarian cancer cells. Pathway network analysis revealed four statistically significant antiviral pathways, including HCMV, HPV, EBV, and HIV1 infection pathways. Interestingly, compared with the reported 284 SARS‐CoV‐2/COVID‐19‐related genes from GencLip3, we identified 52 SARS‐CoV‐2/COVID‐19‐related protein alterations when treated with and without ivermectin. Protein–protein network (PPI) was constructed based on the interactions between 284 SARS‐CoV‐2/COVID‐19‐related genes and between 52 SARS‐CoV‐2/COVID‐19‐related proteins regulated by ivermectin. Molecular complex detection analysis of PPI network identified three hub modules, including cytokines and growth factor family, MAP kinase and G‐protein family, and HLA class proteins. Gene Ontology analysis revealed 10 statistically significant cellular components, 13 molecular functions, and 11 biological processes. These findings demonstrate the broad‐spectrum antiviral property of ivermectin benefiting for COVID‐19 treatment in the context of predictive, preventive, and personalized medicine in virus‐related diseases.
Keywords: ivermectin, quantitative proteomics, SARS‐CoV‐2/COVID‐19, stable isotope labeling by amino acids in cell culture, virus‐related pathways

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536980/
Summary:
  • 1.
    This study sought to identify ivermectin‐related virus infection pathway alterations in human cells.
  • 2.
    Quantitative proteomics revealed that ivermectin‐related proteins are involved in four statistically significant antiviral pathways, including human cytomegalovirus (HCMV), human papillomavirus (HPV), Epstein–Barr virus (EBV), human immunodeficiency virus 1 (HIV1), and COVID‐19 infection pathways.
  • 3.
    We identified 52 severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)/COVID‐19‐related protein alterations when treated with and without ivermectin, and these proteins were involved in cytokines and growth factor family, MAP kinase and G‐protein family, and HLA class proteins.
  • 4.
    These findings demonstrate the broad‐spectrum antiviral property of ivermectin benefiting for COVID‐19 treatment in the context of predictive, preventive, and personalized medicine in virus‐related diseases.
Emphasis mine.
 
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junkcrap50

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Other quotes from paper:
3.4. The overlap of 52 ivermectin‐regulated SARS‐CoV‐2‐related proteins among virus‐related pathways
The overlap of ivermectin‐regulated SARS‐CoV‐2‐related proteins on virus‐related pathways was constructed by Venn diagrams (Figure 3a and Table S5), and four ivermectin‐regulated SARS‐CoV‐2‐related proteins were identified among those five groups (EBV, HCMV, HIV, HPV, and SARS‐COV‐2), including HLA‐A, AKT1, NFKB1, and CASP3. SILAC quantitative proteomics analysis revealed a broad‐spectrum antiviral property of ivermectin, so further study of the overlap of ivermectin‐regulated SARS‐CoV‐2‐related proteins among virus‐related pathways might be important
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Figure 3
The overlapping analysis of ivermectin‐regulated SARS‐CoV‐2‐related proteins among virus‐related pathways and their chromosomal locations. (a) The overlap of ivermectin‐regulated SARS‐CoV‐2‐related proteins among virus‐related pathways was constructed by Venn diagrams. (b) The chromosomal locations corresponding with protein expression of 52 SARS‐CoV‐2‐related proteins that were regulated by ivermectin. EBV, Epstein–Barr virus; HCMV, human cytomegalovirus; HPV, human papillomavirus; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
In terms of EBV infection pathway, a total of 79 ivermectin‐related proteins have been identified. Some of them have been reported mediated by ivermectin in previous studies. For example, ivermectin was proved to inhibit nitric oxide synthase and cyclooxygenase‐2 enzymes by inhibiting phosphorylation of mitogen‐activated protein kinases (MAPK8) after stimulated cells with LPS (X. Zhang et al., 2009).
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Their study on how ivermectin affected the protenomic profiles & molecular network alterations might be helpful when comparing with all the recently done proteonomic and metabolomic studies in CFS. This study said it turns out there was overlap between these other viral pathways protein changes and COVID proteins. Does Long Covid (and thus CFS) have the same proteomoics?
 

Hip

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Although ivermectin has potent antiviral properties in vitro for coronavirus, unfortunately those antiviral effects do not manifest in vivo, because the ivermectin concentrations used in vitro (in a cell line) are far to high to obtain in the body.

In other words, at the doses used in humans, you cannot achieve these high in vitro concentrations.

Ivermectin however also has immunomodulatory properties which potentially may help fight coronavirus, even at normal human doses.
 
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