김범규 (충북대학교)

한빛사논문

조회284

김범규Beom Kyu Kim

충북대학교

CV File 66 kb

Adv. Healthc. Mater., Feb 08 2024, | https://doi.org/10.1002/adhm.202302803 Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS-CoV-2 Variants

Jaehyeon Hwang ^{1^a}, Beom Kyu Kim^{2^a}, Seokoh Moon ¹, Wonbeom Park ¹, Kyeong Won Kim ¹, Jeong Hyeon Yoon ¹, Hyunseok Oh^1,3, Sangwon Jung ³, Youngseo Park ¹, Suhyun Kim¹, Misoo Kim ¹, Soomin Kim ¹, Younghun Jung ¹, Myungseo Park ¹, Jun-Ho Kim ⁴, Sang Taek Jung⁵, Sang Jick Kim ⁶, Yong-Sung Kim ⁴, Woo-Jae Chung ¹, Min-Suk Song ², Dae-Hyuk Kweon ^1,3

¹Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

²College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, 28644, Republic of Korea.

³Research Center, Mvrix Inc., Anyang, 14058, Republic of Korea.

⁴Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea.

⁵Department of Biomedical Sciences, Graduate School, Korea University, Seoul, 02841, Republic of Korea.

⁶Synthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea.

^aThese authors contributed equally to this work.

CORRESPONDING AUTHORS : Min-Suk Song, Dae-Hyuk Kweon

Abstract

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent that effectively target multiple viral strains. One promising approach to this problem is to use host cell viral receptors as competitive inhibitors, but the inherent low potency and membrane-bound nature of viral receptors has frustrated this strategy despite its conceptual simplicity. In this study, we show that ACE2 anchored into a planar membrane patch can effectively neutralize all tested SARS-CoV-2 variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses. This article is protected by copyright. All rights reserved.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-14)
연구진국내 연구진
분야 생명과학 > 생물공학

댓글 작성 로그인

CV 열람하기

연락처 보기