cn0c00373_si_001.pdf (1.76 MB)
Considerations around the SARS-CoV‑2 Spike Protein with Particular Attention to COVID-19 Brain Infection and Neurological Symptoms
journal contribution
posted on 2020-07-21, 18:05 authored by Kambiz Hassanzadeh, Helena Perez Pena, Jessica Dragotto, Lucia Buccarello, Federico Iorio, Stefano Pieraccini, Giulio Sancini, Marco FeligioniSpike
protein (S protein) is the virus “key” to infect
cells and is able to strongly bind to the human angiotensin-converting
enzyme2 (ACE2), as has been reported. In fact, Spike structure and
function is known to be highly important for cell infection as well
as for entering the brain. Growing evidence indicates that different
types of coronaviruses not only affect the respiratory system, but
they might also invade the central nervous system (CNS). However,
very little evidence has been so far reported on the presence of COVID-19
in the brain, and the potential exploitation, by this virus, of the
lung to brain axis to reach neurons has not been completely understood.
In this Article, we assessed the SARS-CoV and SARS-CoV-2 Spike protein
sequence, structure, and electrostatic potential using computational
approaches. Our results showed that the S proteins of SARS-CoV-2 and
SARS-CoV are highly similar, sharing a sequence identity of 77%. In
addition, we found that the SARS-CoV-2 S protein is slightly more
positively charged than that of SARS-CoV since it contains four more
positively charged residues and five less negatively charged residues
which may lead to an increased affinity to bind to negatively charged
regions of other molecules through nonspecific and specific interactions.
Analysis the S protein binding to the host ACE2 receptor showed a
30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein.
These results might be useful for understanding the mechanism of cell
entry, blood-brain barrier crossing, and clinical features related
to the CNS infection by SARS-CoV-2.