SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders

Abstract

SARS-CoV-2 is a novel coronavirus that severely affects the respiratory system, is the cause of the COVID-19 pandemic, and is projected to result in the deaths of 2 million people worldwide. Recent reports suggest that SARS-CoV-2 also affects the central nervous system along with other organs. COVID-19-associated complications are observed in older people with underlying neurological conditions like stroke, Alzheimer's disease, and Parkinson's disease. Hence, we discuss SARS-CoV-2 viral replication and its inflammation-mediated infection. This review also focuses on COVID-19 associated neurological complications in individuals with those complications as well as other groups of people. Finally, we also briefly discuss the current therapies available to treat patients, as well as ongoing available treatments and vaccines for effective cures with a special focus on the therapeutic potential of a small 5 amino acid peptide (PHSCN), ATN-161, that inhibits SARS-CoV-2 spike protein binding to both integrin α5β1 and α5β1/hACE2.

Keywords: COVID-19; Fibrosis; Integrins; Neuroinflammation; Neurological disorders; SARS-CoV-2.

Graphical abstract

Fig. 1

Global cumulative COVID-19 confirmed cases as of 12/20/2020. https://www.who.int/publications/m/item/weekly-epidemiological-update---22-december-2020.

Fig. 2

The mechanisms of SARS-CoV-2 infection, replication and nervous system invasion. SARS-CoV-2 that causes COVID-19 may originate from the primary host bats and cross the species barrier to humans. The spike protein on SARS-CoV-2 binds to the cell surface receptor ACE2 and the enzyme TMPRSS2, which aid the virion entry, virion releases its RNA, part of which is translated into proteins, and the RNA are assembled into a new virion in the Golgi and released. Exposure to SARS-CoV-2 induces pulmonary inflammation with immune cell infiltration that promotes inflammatory cytokine storms. The coronaviruses can affect the nervous system through blood circulation and cause neuroinflammation. We identified that ATN-161 inhibits SARS-CoV-2 infection in vitro, where the addition of ATN-161 is proposed to inhibit SARS-CoV-2 spike protein binding to host α5β1 integrin, ACE2, as well as α5β1-ACE2 binding. We hypothesize the potential for the virus to enter brain endothelial cells via ACE2 and α5β1 integrin, and that this could also be blocked by ATN-161. We further hypothesize that ATN-161 might also indirectly block SARS-CoV-2 mediated BBB breakdown and neuro-inflammation.