Friday Hope: Metformin Revisited: Anti-Filopodia Properties

Metformin combined with Nattokinase/Bromelain/NAC as potential Long COVID/Spike Therapeutic

Effects of Metformin on Lamellipodia and Filopodia Formation, Ras-related C3 Botulinum Toxin Substrate 1 (Rac1) and Ras Homolog Gene Family, Member A (RhoA) Expression. (A) HeLa cells were stained with phalloidin-rhodamine (scale bar = 100 μm). (B) and (C) Western blotting and the relative level of Rac1 and RhoA in HaCaT cells after treated with metformin for 24 h. Data are shown as mean ± SEM of four independent experiments, *P<0.001 compared to control.

Metformin has been shown to be a promising therapeutic in the treatment of COVID. It treats the cytokine storm, yes, but moreover it PROTECTS THE MICROVASCULATURE AND PREVENTS SECONDARY FIBROSIS.

A comparison of the multifactorial pathophysiological mechanisms of Covid-19 progression with metformin's well-known pleiotropic properties suggests that the treatment of patients with this drug might be particularly beneficial. Indeed, metformin could alleviate the cytokine storm, diminish virus entry into cells, protect against microvascular damage as well as prevent secondary fibrosis. Although our in-depth analysis covers many potential metformin mechanisms of action, we want to highlight more particularly its unique microcirculatory protective effects since worsening of Covid-19 disease clearly appears as largely due to severe defects in the structure and functioning of microvessels.

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087/

There is another property of Metformin which, I believe, is effective against the Spike protein as well as the virus. Metformin prevents the formation of filopodia. The Spike (and the virus and the Spike’s RNP) uses filopodia to travel, incognito, between cells.

Regarding the effect of metformin on the inhibition of HeLa cells, we further investigated whether metformin affect the formation of lamellipodia and filopodia in HeLa cells. The cells were cultured in the presence or absence of metformin (0-10 mM) for 24 h, the lamellipodia formation and filopodia protrusion were then photographed under fluorescence modes of a microscope using phalloidin assays. Figure 4A showed that HeLa cells in the moving state exhibited a substantial number of filopodia protrusions and lamellipodia formation that were dramatically reduced in response to metformin treatments. The reduction of lamellipodia and filopodia in the cells is probably due to the negative regulatory role of metformin.

Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173373/

A Stealth Weapon of Cellular Mass Destruction: The Spike Protein, its mRNA and Nanotubes

A Stealth Weapon of Cellular Mass Destruction: The Spike Protein, its mRNA and Nanotubes

In light of this additional property of Metformin, I believe that investigating the use of Metformin in combination with Spike degrading therapeutics may indeed resolve, or stop the additional, of Long COVID and Spike Protein exposure. Metformin assists in stopping the “invisible” spread of the virus/Spike Protein and its RNP and Nattokinase/Bromelain/NAC degrades the Spike Protein.

Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2
https://pubmed.ncbi.nlm.nih.gov/36080170/

An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants
https://www.frontiersin.org/articles/10.3389/fphar.2021.717757/full

Taking the approach of stopping the spread Spike Protein by filopodia (and the virus, if it is indeed hiding in reservoirs) and then destroying the Spike Protein may be able to resolve the condition of Long COVID and ameliorate damage done by the Spike Protein.