The phenomenon of protein aggregation is widespread and associated with a wide range of human diseases. Our knowledge on the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated the distribution of aggregation-prone regions in the the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions in these proteomes, and revealed an enhanced aggregation

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... nsity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone regions in the of SARS-CoV-2 proteome, including the signal sequence peptide and fusion peptide 1 of the spike protein, a peptide from the NSP6 protein (NSP6-p), the ORF10 protein, and the NSP11 protein. Our re-sults show that these peptides and proteins form aggregates via a nucleation-dependent mecha-nism. Moreover, we demonstrated that the aggregates of NSP11 are toxic to mammalian cell cultures. These findings provide evidence about the aggregation of proteins in the SARS-CoV-2 proteome.