Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes.

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.

• Authors: Taniya Bhardwaj, Kundlik Gadhave, Shivani K Kapuganti, Prateek Kumar, Zacharias Faidon Brotzakis, Kumar Udit Saumya, Namyashree Nayak, Ankur Kumar, Richa Joshi, Bodhidipra Mukherjee, Aparna Bhardwaj, Krishan Gopal Thakur, Neha Garg, Michele Vendruscolo, Rajanish Giri
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 945 (02 20 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 36806058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Amyloidogenic Proteins
• Proteome

Topics

• Humans
• Animals
• Amyloidogenic Proteins
• Proteome
• SARS-CoV-2
• Severe acute respiratory syndrome-related coronavirus
• COVID-19
• Mammals