Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms

Abdul Mannan Baig, Areeba Khaleeq, Usman Ali, Hira Syeda, Abdul Mannan Baig, Areeba Khaleeq, Usman Ali, Hira Syeda

Abstract

The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host-virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

Keywords: ACE2 tissue distribution; COVID-19; Coronavirus; SARS-CoV-2; host−virus interaction; spike protein.

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Tissue distribution of ACE2 receptors in humans. Viremia (A) disseminates the COVID-19 virus throughout the body via the bloodstream (B). Neurotropism may occur via circulation and/or an upper nasal trancribrial route that enables the COVID-19 to reach the brain (C) and bind and engage with the ACE2 receptors (D, blue). COVID-19 docks on the ACE2 via spike protein (D, golden spikes). Shown are lungs, heart, kidneys, intestines, brain, and testicles that are well-known to express ACE2 receptors and are possible targets of COVID-19.
Figure 2
Figure 2
(A) Sequence alignment of COVID-19 RBD subdomain-1 (319th to 591st) amino acid (top row) with the bat and SARS-CoV spike protein (middle and bottom row) that were fetched from BLASTp results of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acids. Note horizontal arrows that show areas of contrast between the sequences. (A1) Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template (6vsb.1. A)-based model of the COVID-19 virus spike glycoprotein. (B). Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template-(5x5b.1.A) based model of the prefusion structure of SARS-CoV spike glycoprotein in conformation 2 (B1) with 73.96% sequence identity. [Uniprot and SWISS-MODEL automated server were used for sequence alignments and development of the templates and models, respectively.]

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Source: PubMed

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