Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

Islam, S.; Charnley, M.; Bindra, G.; Ratcliffe, J.; Zhou, J.; Mezzenga, R.; Hulett, M. D.; Han, K.; Berryman, J. T.; Reynolds, N. P.

doi:10.1101/2021.11.24.469537

bioRxiv · 10.1101/2021.11.24.469537

Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

Islam, S.·Charnley, M.·Bindra, G.·Ratcliffe, J.·Zhou, J.·Mezzenga, R.·Hulett, M. D.·Han, K.·Berryman, J. T.·Reynolds, N. P.

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Abstract

COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called long COVID). These neurological symptoms are thought to be caused by brain inflammation, triggered by the virus infecting the central nervous system of COVID-19 patients, however we still dont fully understand the mechanisms for these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimers and Parkinsons in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides and discovered that they do rapidly self-assemble into amyloid. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID, especially those symptoms which are novel to long COVID in contrast to other post-viral syndromes.

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Islam, S., Charnley, M., Bindra, G., Ratcliffe, J., Zhou, J., Mezzenga, R., Hulett, M. D., Han, K., Berryman, J. T., Reynolds, N. P.. 2021-11-24. Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19. https://doi.org/10.1101/2021.11.24.469537

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