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정효기Hyo Gi Jung

고려대학교

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Nat. Commun., 07 March 2024 | https://doi.org/10.1038/s41467-024-46296-7 Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2

Dongtak Lee ^1,2,3,11, Hyo Gi Jung^1,4,11, Dongsung Park ^1,5,11, Junho Bang ^1,4, Da Yeon Cheong ^6,7, Jae Won Jang ^1,4, Yonghwan Kim ^1,4, Seungmin Lee ^1,8, Sang Won Lee ^1,9, Gyudo Lee ^6,7, Yeon Ho Kim ^1,4, Ji Hye Hong ^1,8, Kyo Seon Hwang ^5,* , Jeong Hoon Lee^8,* & Dae Sung Yoon ^1,4,10,*

¹School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.
²Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.
³Harvard Medical School, Boston, MA 02115, USA.
⁴Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, South Korea.
⁵Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul 02447, South Korea.
⁶Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea.
⁷Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea.
⁸Department of Electrical Engineering, Kwangwoon University, Seoul 01897, South Korea.
⁹Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA.
¹⁰Astrion Inc, Seoul 02841, South Korea.
¹¹These authors contributed equally: Dongtak Lee, Hyo Gi Jung, Dongsung Park.

^*Corresponding authors: correspondence to Kyo Seon Hwang, Jeong Hoon Lee or Dae Sung Yoon

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 (M^pro) 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 M^pro-inhibitor screening platform to evaluate the efficacies of M^pro inhibitors based on M^pro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and M^pro-cleavage sequence, mimicking in vivo viral replication process mediated by M^pro. By measuring the proteolytic activity of M^pro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of M^pro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering M^pro inhibitors and may accelerate the development of therapeutics against COVID-19.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-08)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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