The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Simple Summary There is limited information on how SARS-CoV-2 reaches the brain. Thus, this paper examines how, during co-infection, a protease-secreting microbe may facilitate brain invasion by SARS-CoV-2. An understanding of this potential invasion mechanism could lead to better SARS-CoV-2 intervention measures. SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensin-converting 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. With this contribution, we explore how, in the context of a microbial co-infection using a cryptococcal co-infection as a model, SARS-CoV-2 could reach the brain. We theorise that the secretion of proteases by disseminated fungal cells might also activate the S2 domain of the viral spike glycoprotein for membrane fusion with brain endothelial cells leading to endocytosis. Understanding this potential invasion mechanism could lead to better SARS-CoV-2 intervention measures, which may also be applicable in instances of co-infection, especially with protease-secreting pathogens.