SARS-CoV-2 S1 spike protein peptides inhibit alpha 7 nAChRs and are counteracted by a PAM at alpha 7

Abstract

Clinical observations of low smoking prevalence among hospitalized COVID-19 patients and identification of snake “toxin-like” peptide sequences in SARS-CoV-2 spike protein, led Changeux et al (2020 C R Biol) and Farselinos et al (2020 J Toxicol) [C & F] to propose that hyper-inflammation of severe COVID-19 reflects dysfunction of the “cholinergic anti-inflammatory pathway” (CAP). In seminal CAP studies, Tracey et al (2002, 2012) found that vagal nerve release of acetylcholine (Ach) suppressed activation of NF-κB and production of proinflammatory cytokines in α7 nicotinic Ach receptor- (α7 nAChR-) expressing macrophages.