Implications of the SARS-CoV-2 spike protein interaction with type-1 macrophages via α7-nAChR.

Abstract

The human immune system has a generic response strategy to viral infections that begins with local inflammation at the infected site along with the initiation of a primary innate immune response. Beyond a certain threshold, innate immune cells cannot handle the infection, and they call upon adaptive immunity. The innate cells then take up their role in “The Resolution of Inflammation”. The recognition of the SARS-CoV-2 antigen triggers an eicosanoid storm and initiates a robust inflammatory response, leading to a sustained cytokine storm that interferes with the activation of adaptive immune cells, specifically BCL6 B cells. The mechanism of this interaction, and hence the pathogenesis of the virus with the immune system, is yet to be determined. In silico studies predict a direct viral interaction with type 1 resident macrophages, which could initiate the cascade of events described above. The macrophage population being the target would also explain why older age groups are relatively more susceptible to the virus. Here, we review the interaction of the SARS-CoV-2 spike protein via a cryptic epitope with the α7-nAChR in Type-1 macrophages, discuss the implications it might have on our approach to the generic treatment of COVID-19 patients, and present better prospects for the design and dissemination of more effective vaccines and their importance.