creators_name: Bhardwaj, Taniya creators_name: Gadhave, Kundlik creators_name: Kapuganti, Shivani K creators_name: Kumar, Prateek creators_name: Brotzakis, Z.F creators_name: Saumya, Kumar Udit creators_name: Nayak, Namyashree creators_name: Kumar, Ankur creators_name: Joshi , Richa creators_name: Mukherjee, Bodhidipra creators_name: Bhardwaj, Aparna creators_name: Thakur, Krishan Gopal creators_name: Garg, Neha creators_name: Vendruscolo, Michele creators_name: Giri, Rajanish type: article datestamp: 2024-07-16 02:27:59 lastmod: 2024-07-16 02:27:59 metadata_visibility: show title: Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes ispublished: pub subjects: QR note: The copyright of this article belongs to Nature Pub. Group abstract: The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in 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 (APRs) in these proteomes and revealed a strong aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV and SARS-CoV-2 proteins and protein regions, including the signal sequence peptide and fusion peptides 1 and 2 of the spike protein, a peptide from the NSP6 protein, and the ORF10 and NSP11 proteins. Our results show that these peptides and proteins can form amyloid aggregates. We used circular dichroism spectroscopy to reveal the presence of β-sheet rich cores in aggregates and X-ray diffraction and Raman spectroscopy to confirm the formation of amyloid structures. Furthermore, we demonstrated that SARS-CoV-2 NSP11 aggregates are toxic to mammalian cell cultures. These results motivate further studies about the possible role of aggregation of SARS proteins in protein misfolding diseases and other human conditions. date: 2023-02-20 date_type: published publication: Nature communications volume: 14 number: 1 publisher: Nature Pub. Group id_number: 10.1038/s41467-023-36234-4 refereed: TRUE issn: 2041-1723 official_url: https://www.nature.com/articles/s41467-023-36234-4 citation: Bhardwaj, Taniya and Gadhave, Kundlik and Kapuganti, Shivani K and Kumar, Prateek and Brotzakis, Z.F and Saumya, Kumar Udit and Nayak, Namyashree and Kumar, Ankur and Joshi , Richa and Mukherjee, Bodhidipra and Bhardwaj, Aparna and Thakur, Krishan Gopal and Garg, Neha and Vendruscolo, Michele and Giri, Rajanish (2023) Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes. Nature communications, 14 (1). ISSN 2041-1723