한빛사논문
- 조회97
Yuri Seo 1,2,9, Yejin Jang 3,9, Seon-gyeong Lee 2,4,8,9, Joon Ho Rhlee 5, Sukyeong Kong 2,6, Thi Tuyet Hanh Vo 1, Myung hun Kim 1, Myoung Kyu Lee 3, Byungil Kim 3, Sung You Hong 2,5, Meehyein Kim 3,7,*, Joo-Yong Lee 1,* and Kyungjae Myung 2,6,*
1Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea.
2Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, Republic of Korea.
3Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
4Department of Biological Science, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
5Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
6Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
7Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
8Present address: CasCure Therapeutics, Seoul, Republic of Korea.
9These authors contributed equally: Yuri Seo, Yejin Jang, Seon-gyeong Lee.
*Corresponding authors: correspondence to Meehyein Kim, Joo-Yong Lee or Kyungjae Myung
Abstract
The SARS-CoV-2 pandemic has had an unprecedented impact on global public health and the economy. Although vaccines and antivirals have provided effective protection and treatment, the development of new small molecule-based antiviral candidates is imperative to improve clinical outcomes against SARS-CoV-2. In this study, we identified UNI418, a dual PIKfyve and PIP5K1C inhibitor, as a new chemical agent that inhibits SARS-CoV-2 entry into host cells. UNI418 inhibited the proteolytic activation of cathepsins, which is regulated by PIKfyve, resulting in the inhibition of cathepsin L-dependent proteolytic cleavage of the SARS-CoV-2 spike protein into its mature form, a critical step for viral endosomal escape. We also demonstrated that UNI418 prevented ACE2-mediated endocytosis of the virus via PIP5K1C inhibition. Our results identified PIKfyve and PIP5K1C as potential antiviral targets and UNI418 as a putative therapeutic compound against SARS-CoV-2.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-01)
- 국내 연구진
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