Aspirin: Inhibiting NLRP3 Inflammasome and Protecting Against COVID/Spike Endothelial Injury
Aspirin has also been shown to have significant prophylactic effects if taken before COVID infection.
Given all the recent evidence that the Spike Protein induces Cardiac Fibrosis by activating the NLRP3 inflammasome, I began a search for therapeutics to ameliorate this effect. In Aspirin not only have we found a safe, readily available therapeutic which inhibits the NLRP3 inflammasome, but also protects against endothelial damage caused by COVID infection and the Spike Protein.
First, generally speaking, Aspirin appears to be tailor-made for protecting the endothelium against Spike Protein injury and damage. The Spike Protein is a “lipopolysaccharide delivery system” in and of itself, causing the aforementioned damage.
Accumulating evidence indicates a potential role for bacterial lipopolysaccharide (LPS) in the overactivation of the immune response during SARS-CoV-2 infection. LPS is recognized by Toll-like receptor 4, mediating proinflammatory effects. We previously reported that LPS directly interacts with SARS-CoV-2 spike (S) protein and enhances proinflammatory activities. Using native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry, we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S protein. Molecular simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1, suggesting a role as an intermediate in LPS transfer. Congruently, nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells is strongly boosted by S2. Using NF-κB reporter mice followed by bioimaging, a boosting effect was observed for both S1 and S2, with the former potentially facilitated by proteolysis. The Omicron S variant binds to LPS, but with reduced affinity and LPS boosting in vitro and in vivo. Taken together, the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation.
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https://wmcresearch.substack.com/p/friday-hope-aspirin-inhibiting-nlrp3
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