Coronavirus Greece - Research and Innovation

We are a group of experienced researchers from GREECE. We have identified an interaction between SARS-CoV-2 SPIKE Glycoprotein and the nicotinic cholinergic pathway. This interaction is between the SPIKE Glycoprotein and the main component of this pathway, the neuronal type nicotinic acetylcholine receptors (nAChRs). This interaction is happening through a well characterized epitope, in the beginning of the Receptor Binding Domain, mainly composed by the aminoacids aa375-390. Antibodies against this epitope (like the well known anti SARS antibody CR3022) can work protectively. We are working to characterize this interaction, human recombinant antibodies are produced and the diagnostic/prognostic importance of this finding is further studied.

Publications

  • Konstantinos Farsalinos, Athina Angelopoulou, Nikos Alexandris, Konstantinos Poulas, COVID-19 and the nicotinic cholinergic system. European Respiratory Journal 2020; DOI:10.1183/13993003.01589-2020 (link)
  • Konstantinos Farsalinos, Anastasia Barbouni, Raymond Niaura, Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option? Intern Emerg Med.2020 May 9;1-8. DOI: 10.1007/s11739-020-02355-7. (link)
  • Konstantinos Farsalinos, Anastasia Barbouni, Konstantinos Poulas, Riccardo Polosa, Pasquale Caponnetto, Raymond NiauraFirst, "Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis Therapeutic Advances in Chronicle Disease 11, June 25, 2020 DOI:2040622320935765 (link)

MAIN RESEARCH FINDINGS

The number of smokers showing severe COVID-19 that requires hospitalization is by far lower than expected For the very few smokers who end up in the hospital with COVID-19, the odds of having an adverse outcome is increased compared to non-smokers. Potential benefits of Nicotine for COVID-19 disease

MAIN HYPOTHESIS

  • The clinical manifestations of cytokine storm observed in COVID-19 could be linked to a dysfunction of the cholinergic anti-inflammatory pathway.
  • The cholinergic anti-inflammatory pathway is an important immune-regulating system mediated by nAChRs, can control inflammation and function as an immunomodulator through a bi-directional communication between the immune and nervous systems.
  • Nicotine may be beneficial for COVID-19 and should be evaluated in clinical trials due to its anti-inflammatory properties.

Potencial interaction with Nicotinic cholinergic System

  • Konstantinos Farsalinos, Raymond Niaura, Jacques Le Houezec, Anastasia Barbouni, Aristidis Tsatsakis, Dimitrios Kouretas, Apostolos Vantarakis, Konstantinos Poulas, Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system, Toxicol Rep. 2020, Apr 30. DOI: 10.1016/j.toxrep.2020.04.012 (link)


COVID-19 UNEXPLAINED SYMPTOMS

  • Severe COVID-19 is characterized by a hyper-inflammatory response (cytokine storm) characterized by the release of pro-inflammatory cytokines.

    • Several patients experience neurological symptoms that could be explained by the invasion of the virus to the terminal area of afferent vagus fibers or the origin of the efferent vagus fibers, further dysregulation the inflammatory response.
    • Anosmia has been experienced by several patients, a phenomenon that has been observed in patients with Parkinson’s disease and is caused by impaired cholinergic transmission.

NEXT STEPS

  • Research in order to identify the direct interaction between SPIKE and nAChRs
  • Ongoing Clinical trials for nicotine and varenicline
  • Peptide synthesis – Competition experiments
    • ELISA development – Biomarker charactirization
  • Mouse, Human, Humanized antibody production

THE TEAM

Konstantinos Poulas

Konstantinos Poulas

Biochemistry -Immunology

Konstantinos Farsalinos

Konstantinos Farsalinos

Cardiology – Nicotine

Socrates Tzartos

Socrates
Tzartos

Immunology – Acetylcholine Receptors

Elias Eliopoulos

Elias
Eliopoulos

Biochemistry – Bioinformatics

John Tzartos

John
Tzartos

Neurology - Neuroimmunology

Ehud Almon

Ehud
Almon

Serial Enterpreneur