Cytotoxicity of the Spike Protein

Microbiol Spectr. 2021 Nov-Dec; 9(3): e00735-21.
Published online 2021 Dec 22. doi: 10.1128/Spectrum.00735-21
PMCID: PMC8693925
PMID: 34935423
SARS-CoV-2 Spike Protein Destabilizes Microvascular Homeostasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693925/

Cells. 2021 Dec; 10(12): 3279.
Published online 2021 Nov 23. doi: 10.3390/cells10123279
PMCID: PMC8699033
PMID: 34943787
SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699033/

Mol Neurobiol. 2022; 59(1): 445–458.
Published online 2021 Oct 28. doi: 10.1007/s12035-021-02593-6
PMCID: PMC8551352
PMID: 34709564
SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551352/

FASEB J. 2021 Sep; 35(9): e21801.
Published online 2021 Aug 8. doi: 10.1096/fj.202002742RR
PMCID: PMC8441663
PMID: 34365657
Spike protein of SARS‐CoV‐2 activates macrophages and contributes to induction of acute lung inflammation in male mice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441663/

Nat Med. 2005; 11(8): 875–879.
Published online 2005 Jul 10. doi: 10.1038/nm1267
PMCID: PMC7095783
PMID: 16007097
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095783/

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world^1,2,3. A new coronavirus (SARS-CoV) was identified as the SARS pathogen^4,5,6,7, which triggered severe pneumonia and acute, often lethal, lung failure⁸. Moreover, among infected individuals influenza such as the Spanish flu^9,10 and the emergence of new respiratory disease viruses^11,12 have caused high lethality resulting from acute lung failure¹³. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor¹⁴. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.