Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

Mirren Charnley, Saba Islam, Guneet K. Bindra, Jeremy Engwirda, Julian Ratcliffe, Jiangtao Zhou, Raffaele Mezzenga, Mark D. Hulett, Kyunghoon Han, Joshua T. Berryman () and Nicholas P. Reynolds ()
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Mirren Charnley: Swinburne University of Technology
Saba Islam: La Trobe Institute for Molecular Science, La Trobe University
Guneet K. Bindra: La Trobe Institute for Molecular Science, La Trobe University
Jeremy Engwirda: La Trobe Institute for Molecular Science, La Trobe University
Julian Ratcliffe: La Trobe University Bioimaging Platform
Jiangtao Zhou: ETH Zurich
Raffaele Mezzenga: ETH Zurich
Mark D. Hulett: La Trobe Institute for Molecular Science, La Trobe University
Kyunghoon Han: University of Luxembourg
Joshua T. Berryman: University of Luxembourg
Nicholas P. Reynolds: La Trobe Institute for Molecular Science, La Trobe University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.

Date: 2022
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DOI: 10.1038/s41467-022-30932-1

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