journal contribution
posted on 2022-06-30, 06:25 authored by Mirren Charnley, Saba Islam, Guneet BindraGuneet Bindra, Jeremy EngwirdaJeremy Engwirda, Julian RatcliffeJulian Ratcliffe, Jiangtao Zhou, Raffaele Mezzenga, Mark HulettMark Hulett, Kyunghoon Han, Joshua T Berryman, Nicholas ReynoldsNicholas Reynolds 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.
Funding
N.P.R. would like to acknowledge The La Trobe Institute of Molecular Sciences (LIMS) for the receipt of a Nicholas Hoogenraad fellowship, and the CASS foundation for partially funding this work through a philanthropic grant (#10053, `Determining the role of protein aggregation in COVID-19'). N.P.R. would also like to acknowledge that Fig. 6 was created using Biorender.com. The authors thank Dr Susi Seibt for assistance on the SAXS/WAXS beamline at the Australian Synchrotron. This research was undertaken, in part, on the SAXS/WAXS beamline at the Australian Synchrotron, part of ANSTO. Molecular dynamics calculations made use of the HPC service of the University of Luxembourg64. The project was part-funded by grant C20/MS/14588607 of the Fonds Nationale de la Recherche, Luxembourg.
History
Publication Date
2022-06-13Journal
Nature CommunicationsVolume
13Issue
1Article Number
3387Pagination
11p.Publisher
Springer NatureISSN
2041-1723Rights Statement
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