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 being able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as it has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as 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 few evidence have been so far reported on the presence of COVID-19 in the brain and the potential exploitation, by this virus, of lung to brain axis to reach neurons has not 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 non-specific and specific interactions. Analyzing of the S protein binds to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than 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.