Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research

Int J Mol Sci. 2022 Jan 8;23(2):672. doi: 10.3390/ijms23020672.

Abstract

The appearance of the SARS-CoV-2 virus initiated many studies on the effects of the virus on the human body. So far, its negative influence on the functioning of many morphological and physiological units, including the nervous system, has been demonstrated. Consequently, research has been conducted on the changes that SARS-CoV-2 may cause in the cholinergic system. The aim of this study is to review the latest research from the years 2020/2021 regarding disorders in the cholinergic system caused by the SARS-CoV-2 virus. As a result of the research, it was found that the presence of the COVID-19 virus disrupts the activity of the cholinergic system, for example, causing the development of myasthenia gravis or a change in acetylcholine activity. The SARS-CoV-2 spike protein has a sequence similar to neurotoxins, capable of binding nicotinic acetylcholine receptors (nAChR). This may be proof that SARS-CoV-2 can bind nAChR. Nicotine and caffeine have similar structures to antiviral drugs, capable of binding angiotensin-converting enzyme 2 (ACE 2) epitopes that are recognized by SARS-CoV-2, with the potential to inhibit the formation of the ACE 2/SARS-CoV-2 complex. The blocking is enhanced when nicotine and caffeine are used together with antiviral drugs. This is proof that nAChR agonists can be used along with antiviral drugs in COVID-19 therapy. As a result, it is possible to develop COVID-19 therapies that use these compounds to reduce cytokine production. Another promising therapy is non-invasive stimulation of the vagus nerve, which soothes the body's cytokine storm. Research on the influence of COVID-19 on the cholinergic system is an area that should continue to be developed as there is a need for further research. It can be firmly stated that COVID-19 causes a dysregulation of the cholinergic system, which leads to a need for further research, because there are many promising therapies that will prevent the SARS-CoV-2 virus from binding to the nicotinic receptor. There is a need for further research, both in vitro and in vivo. It should be noted that in the functioning of the cholinergic system and its connection with the activity of the COVID-19 virus, there might be many promising dependencies and solutions.

Keywords: COVID-19; SARS-CoV-2; acetylcholine; acetylcholinesterase; cholinergic system; nicotinic receptors.

Publication types

  • Review

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • COVID-19 / complications*
  • COVID-19 / virology*
  • Cholinergic Neurons / virology*
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / virology
  • Humans
  • Myasthenia Gravis / virology
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome / virology
  • Vagus Nerve / drug effects
  • Vagus Nerve / virology

Substances

  • Acetylcholinesterase

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related