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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
    1. 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.
    2. Zhenming Jin & Xiaoyu Du & Yechun Xu & Yongqiang Deng & Meiqin Liu & Yao Zhao & Bing Zhang & Xiaofeng Li & Leike Zhang & Chao Peng & Yinkai Duan & Jing Yu & Lin Wang & Kailin Yang & Fengjiang Liu & Re, 2020. "Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors," Nature, Nature, vol. 582(7811), pages 289-293, June.
    3. 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.
    4. Britton Boras & Rhys M. Jones & Brandon J. Anson & Dan Arenson & Lisa Aschenbrenner & Malina A. Bakowski & Nathan Beutler & Joseph Binder & Emily Chen & Heather Eng & Holly Hammond & Jennifer Hammond , 2021. "Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Kangsa Amporndanai & Xiaoli Meng & Weijuan Shang & Zhenmig Jin & Michael Rogers & Yao Zhao & Zihe Rao & Zhi-Jie Liu & Haitao Yang & Leike Zhang & Paul M. O’Neill & S. Samar Hasnain, 2021. "Inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives," Nature Communications, Nature, vol. 12(1), pages 1-7, 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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