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

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 Hoon Lee () and Dae Sung Yoon ()
Additional contact information
Dongtak Lee: Korea University
Hyo Gi Jung: Korea University
Dongsung Park: Korea University
Junho Bang: Korea University
Da Yeon Cheong: Korea University
Jae Won Jang: Korea University
Yonghwan Kim: Korea University
Seungmin Lee: Korea University
Sang Won Lee: Korea University
Gyudo Lee: Korea University
Yeon Ho Kim: Korea University
Ji Hye Hong: Korea University
Kyo Seon Hwang: Kyung Hee University
Jeong Hoon Lee: Kwangwoon University
Dae Sung Yoon: Korea University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46296-7

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