Activation of the SARS-CoV-2 spike protein by 𝘤𝘳𝘺𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘯𝘦𝘰𝘧𝘰𝘳𝘮𝘢𝘯𝘴 secreted proteases

Abstract

SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensinconverting enzyme (ACE2) expression cells. Of interest herein is the ability of the virus to exhibit neurotropism. However, there is limited information on how this virus invades the brain. This contribution explores how, in the context of a microbial co-infection (using a cryptococcal co-infection as a model), SARS-CoV-2 could reach the brain. It was theorised that the secretion of proteases by disseminated fungal cells might also activate the viral spike glycoprotein for membrane fusion with brain endothelial cells, leading to endocytosis. Understanding this potential invasion mechanism could lead to better SARSCoV-2 intervention measures, which may also be applicable in instances of co-infection, especially with protease-secreting pathogens.