Application of Sigma-1 Receptor modulators in SARS-Cov2 Spike Protein-Induced Neuroinflammation Models for the treatment of neurological symptoms in long COVID-19
Thesis supervisor: Lívia Fülöp
Location of studies (in Hungarian): University of Szeged Faculty of Medicine Department of Medical Chemistry Abbreviation of location of studies: OVI
Description of the research topic:
The greatest challenge of 2020 was the global viral pandemic caused by SARS-Cov2. With the constantly increasing number of patients suffering from COVID-19 becomes also obvious that weeks or months after the acute phase of COVID-19, a considerable part of the patients still has symptoms typical of so-called long COVID-19. The symptoms can be assigned presumably as part of a syndrome called Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), for which effective therapies are still missing. Sigma-1 receptor (Sig1R) modulators (mainly agonists) are intensively studied for the treatment of acute COVID-19, possibly those used already as accepted medicaments, like fluvoxamine, which possess promising effects on the inflammation in the infected organs. However, Sig1R modulators haven’t been examined, regarding their effects on neuroinflammation in long COVID19, yet. In our project, we aim to study the mechanisms of known Sig1R modulators in model systems, in which neuroinflammation will be induced by applying the spike (S) protein of SARS-Cov2 either in vitro on human astrocytes or in vivo by injecting it intracerebroventricularly or intrahippocampally in K18-hAce2 transgenic mice. The effect of S protein exerted on the downstream endoplasmic reticulum (ER) stress pathways and on consequent cytokine-activation will be modulated by the known agonists and antagonists. In case of positive results, selected modulators might serve as promising therapeutics for the treatment of neurological symptoms in long COVID-19.
Required language skills: english Number of students who can be accepted: 1
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