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

Author

Listed:
  • Taniya Bhardwaj

    (Indian Institute of Technology Mandi)

  • Kundlik Gadhave

    (Indian Institute of Technology Mandi)

  • Shivani K. Kapuganti

    (Indian Institute of Technology Mandi)

  • Prateek Kumar

    (Indian Institute of Technology Mandi)

  • Zacharias Faidon Brotzakis

    (University of Cambridge)

  • Kumar Udit Saumya

    (Indian Institute of Technology Mandi)

  • Namyashree Nayak

    (Indian Institute of Technology Mandi)

  • Ankur Kumar

    (Indian Institute of Technology Mandi)

  • Richa Joshi

    (Indian Institute of Technology Mandi)

  • Bodhidipra Mukherjee

    (Indian Institute of Technology Mandi)

  • Aparna Bhardwaj

    (Indian Institute of Technology Mandi)

  • Krishan Gopal Thakur

    (CSIR-Institute of Microbial Technology)

  • Neha Garg

    (Banaras Hindu University)

  • Michele Vendruscolo

    (University of Cambridge)

  • Rajanish Giri

    (Indian Institute of Technology Mandi)

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.

Suggested Citation

  • Taniya Bhardwaj & Kundlik Gadhave & Shivani K. Kapuganti & Prateek Kumar & Zacharias Faidon Brotzakis & Kumar Udit Saumya & Namyashree Nayak & Ankur Kumar & Richa Joshi & Bodhidipra Mukherjee & Aparna, 2023. "Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36234-4
    DOI: 10.1038/s41467-023-36234-4
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    1. Kariem Ezzat & Maria Pernemalm & Sandra Pålsson & Thomas C. Roberts & Peter Järver & Aleksandra Dondalska & Burcu Bestas & Michal J. Sobkowiak & Bettina Levänen & Magnus Sköld & Elizabeth A. Thompson , 2019. "The viral protein corona directs viral pathogenesis and amyloid aggregation," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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    Cited by:

    1. Dongtak Lee & Hyo Gi Jung & Dongsung Park & Junho Bang & Da Yeon Cheong & Jae Won Jang & Yonghwan Kim & Seungmin Lee & Sang Won Lee & Gyudo Lee & Yeon Ho Kim & Ji Hye Hong & Kyo Seon Hwang & Jeong Hoo, 2024. "Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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