Spike S1 peptide associated neuroinflammatory and cytokine induction is associated with modified behavior in in vivo models

Abstract

AbstractBackgroundCoronavirus disease (COVID‐19), a severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) is a damaging illness leading to severe health crisis and economic crisis worldwide. Numerous brain complication has been reported in COVID‐19 patients and surprisingly has persisted after COVID‐19 infection recovery in patients. The underlying mechanism are not clear. So far, there is no proper therapeutic strategy against COVID‐19 and its complications on the brain.MethodInitially we validate the effect of recombinant Spike S1 in A5339 cells (Paidi, Jana et al. 2021, Paidi, Jana et al. 2021, Paidi, Jana et al. 2021) and as well as mouse primary astrocyte cultures, in terms of cytokine induction and neuroinflammatory markers. In the current study, mice were administered recombinant spike S1 intranasally for 14 days. Initially we evaluated the physiological and behavioral alteration for 12 days. SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 (ACE2) for entering host cells, we so investigate the lung histology and its cytokine induction. Further, we evaluate the cytokine and neuroinflammatory levels in the brain, and its relevance to behavioral modifications in the mouse.ResultIn the present study, Spike S1 treatment prominently elevate the cytokine levels and inflammatory markers in invitro models. Intranasal intoxication of C57/BL6 mice with recombinant SARS‐CoV‐2 spike S1 led to fever, increase in IL‐6 in the lungs and brain. We found that the impairment in spatial learning memory functions and motor disabilities, mimic some of the important symptoms of COVID‐19. Our studies show Spike S1 induced cytokine levels in lungs and as well as in the brain.ConclusionOur results suggest a simple, but reliable means of developing a Spike S1 mediated in vivo model which exhibits severe lung pathology and reinforce the validity of this animal model to study COVID‐19 pathogenesis and potential therapies. Keywords Spike S1, COVID‐19; IL‐6; Cognitive functions; Motor disabilities, Cytokine induction;