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Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2

Author

Listed:
  • Dongtak Lee

    (Korea University
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Hyo Gi Jung

    (Korea University
    Korea University)

  • Dongsung Park

    (Korea University
    Kyung Hee University)

  • Junho Bang

    (Korea University
    Korea University)

  • Da Yeon Cheong

    (Korea University
    Korea University)

  • Jae Won Jang

    (Korea University
    Korea University)

  • Yonghwan Kim

    (Korea University
    Korea University)

  • Seungmin Lee

    (Korea University
    Kwangwoon University)

  • Sang Won Lee

    (Korea University
    Terasaki Institute for Biomedical Innovation)

  • Gyudo Lee

    (Korea University
    Korea University)

  • Yeon Ho Kim

    (Korea University
    Korea University)

  • Ji Hye Hong

    (Korea University
    Kwangwoon University)

  • Kyo Seon Hwang

    (Kyung Hee University)

  • Jeong Hoon Lee

    (Kwangwoon University)

  • Dae Sung Yoon

    (Korea University
    Korea University
    Astrion Inc)

Abstract

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (Mpro) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46296-7
    DOI: 10.1038/s41467-024-46296-7
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    References listed on IDEAS

    as
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    2. Dongtak Lee & Dongsung Park & Insu Kim & Sang Won Lee & Wonseok Lee & Kyo Seon Hwang & Jeong Hoon Lee & Gyudo Lee & Dae Sung Yoon, 2021. "Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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    1. Matthew Gagne & Barbara J. Flynn & Christopher Cole Honeycutt & Dillon R. Flebbe & Shayne F. Andrew & Samantha J. Provost & Lauren McCormick & Alex Ry & Elizabeth McCarthy & John-Paul M. Todd & Saran , 2024. "Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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