Considerations around the SARS-CoV-2 Spike Protein with Particular Attention to COVID-19 Brain Infection and Neurological Symptoms

Autor: Helena Perez Pena, Giulio Sancini, Stefano Pieraccini, Jessica Dragotto, Federico Iorio, Kambiz Hassanzadeh, Marco Feligioni, Lucia Buccarello
Přispěvatelé: Hassanzadeh, K, Perez Pena, H, Dragotto, J, Buccarello, L, Iorio, F, Pieraccini, S, Sancini, G, Feligioni, M
Rok vydání: 2020
Předmět:
Physiology
viruses
Cognitive Neuroscience
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Pneumonia
Viral
Central nervous system
Cell
ACE2
Plasma protein binding
Biology
Biochemistry
Protein Structure
Secondary
Virus
Betacoronavirus
03 medical and health sciences
0302 clinical medicine
BIO/09 - FISIOLOGIA
medicine
Humans
Amino Acid Sequence
skin and connective tissue diseases
Receptor
Pandemics
030304 developmental biology
Sequence (medicine)
0303 health sciences
SARS-CoV-2
Spike Protein
fungi
Brain
COVID-19
Cell Biology
General Medicine
Protein Structure
Tertiary
respiratory tract diseases
Cell biology
body regions
ACE2
Brain
COVID-19
Spike Protein
medicine.anatomical_structure
Spike Glycoprotein
Coronavirus
Nervous System Diseases
Coronavirus Infections
030217 neurology & neurosurgery
Research Article
Zdroj: ACS Chemical Neuroscience
ISSN: 1948-7193
DOI: 10.1021/acschemneuro.0c00373
Popis: Spike 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.
Databáze: OpenAIRE
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