What is a spike protein. Function of spike protein. Spike in other coronaviruses. Discuss past implications of spike in pathologies.

Mention ACE2 affinity relative to SARS spike protein. Specific characteristics including those which point to a lab origin. Specific and detail ACE2 binding information.

Explain spike protein as a target for antibodies and value in vaccine manufacturing.

Detail effects of ACE2 down-regulation and subsequent impact on RAAS. Detail role of Angiotensin 2 in inflammation, clotting, angiogenesis, etc.

AGE/RAGE connection with Ang 2 pathology.

“In addition to eliciting an immune response that suppresses the viral entry, the spike protein produced by the COVID-19 vaccines may also affect the host cells, possibly triggering adverse events.¹⁾

A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination William J. Murphy, Ph.D., and Dan L. Longo, M.D.

https://www.nejm.org/doi/full/10.1056/NEJMcibr2113694

Abstract The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion.

In some cases, the S protein is proteolytically cleaved at the S1–S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment.

Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2′, R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell–cell fusion and pseudovirion entry assays.

We also introduced a furin cleavage site at both the S2′ cleavage site within S2 793-KPTKR-797 (S2′), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2′ position allowed trypsin-independent cell–cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1–S2 position.

Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity. ²⁾

Spike protein clotting

https://www.biorxiv.org/content/10.1101/2021.10.12.464152v1

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902

The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice: https://pubmed.ncbi.nlm.nih.gov/33328624/

The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier: https://pubmed.ncbi.nlm.nih.gov/33053430/

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease: https://www.biorxiv.org/content/10.1101/2020.12.21.423721v2.full.pdf

Clearing up misinformation about the spike protein and COVID vaccines: https://joomi.substack.com/p/coming-soon