Abstract
Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing multiple neurological symptoms with increased neuroinflammation and blood–brain barrier (BBB) damage. The viral spike protein disseminates via circulation during infection, and when reaching the brain could possibly cross the BBB, which was demonstrated in mice. Therefore, its medical relevance is of high importance. The aim of this study was to evaluate the barrier penetration of the S1 subunit of spike protein in model systems of human organs highly exposed to the infection. For this purpose, in vitro human BBB and intestinal barrier cell–culture systems were investigated by an optical biosensing method. We found that spike protein crossed the human brain endothelial cell barrier effectively. Additionally, spike protein passage was found in a lower amount for the intestinal barrier cell layer. These observations were corroborated with parallel specific ELISAs. The findings on the BBB model could provide a further basis for studies focusing on the mechanism and consequences of spike protein penetration across the BBB to the brain.
Highlights
We investigated the passage of the SARS-CoV-2 S1 spike protein across cell culture models of the blood–brain and intestinal barriers by using a sensitive optical biosensor system
The biosensor system was calibrated with control samples of two characteristic spike protein concentrations (2 and 20 μg/mL in 0.1% bovine serum albumin (BSA)-RH buffer, Figure 3)
For the detection of the target spike protein S1 subunit, samples from the bottom compartments of the permeability assays across the blood– brain barrier (BBB) and Caco-2 models were introduced into the measuring arm of the Mach–Zehnder interferometer (MZI) sensor
Summary
At the end of 2019, a novel respiratory coronavirus was reported by Chinese authorities, which we know as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing a global pandemic. Infection occurs primarily by the inhalation of the virus, which can spread through epithelial and endothelial barriers to multiple organs, leading to systemic inflammation [1]. It has been established that the binding of the CoV-2 spike glycoprotein to angiotensin-converting enzyme 2 (ACE2) triggers penetration of the virus into endothelial and epithelial cells [2]. While the S1 subunit of the spike protein is responsible for anchoring the virion by binding to the ACE2 cellular receptor of the host cell, the S2 subunit enhances the fusion of the viral and the host cell membranes. The fusion is mediated by the S2 subunit that is activated by the transmembrane protease serine 2
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