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

Spike protein (S protein) is the virus “key” to infect cells andis able to strongly bind to the human angiotensin-converting enzyme2(ACE2), as has been reported. In fact, Spike structure and function is knownto be highly important for cell infection as well as for entering the brain.Growing evidence indicates that different types of coronaviruses not onlyaffect the respiratory system, but they might also invade the central nervoussystem (CNS). However, very little evidence has been so far reported on thepresence of COVID-19 in the brain, and the potential exploitation, by thisvirus, of the lung to brain axis to reach neurons has not been completelyunderstood. In this Article, we assessed the SARS-CoV and SARS-CoV-2Spike protein sequence, structure, and electrostatic potential using computa-tional approaches. Our results showed that the S proteins of SARS-CoV-2and SARS-CoV are highly similar, sharing a sequence identity of 77%. Inaddition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains fourmore positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind tonegatively charged regions of other molecules through nonspecific and specific interactions. Analysis the S protein binding to thehost ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein. These results might beuseful for understanding the mechanism of cell entry, blood-brain barrier crossing, and clinical features related to the CNS infectionby SARS-CoV-2.