We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A dual inhibitor of PIP5K1C and PIKfyve prevents SARS-CoV-2 entry into cells.
- Authors
Seo, Yuri; Jang, Yejin; Lee, Seon-gyeong; Rhlee, Joon Ho; Kong, Sukyeong; Vo, Thi Tuyet Hanh; Kim, Myung hun; Lee, Myoung Kyu; Kim, Byungil; Hong, Sung You; Kim, Meehyein; Lee, Joo-Yong; Myung, Kyungjae
- 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. UNI418: Novel antiviral agent targeting SARS-CoV-2 entry and endosomal escape The COVID-19 pandemic, triggered by the SARS-CoV-2 virus, underscores the immediate need for effective treatments, particularly for severe cases. Even with vaccines, treatments that block the virus's entry into cells are vital. SARS-CoV-2 enters host cells by attaching to the ACE2 receptor, a process that is a prime target for intervention. This research concentrates on blocking the virus's entry into cells as a potential treatment method. The study is an experiment using cellular models to assess the effectiveness of a new compound, UNI418, in preventing SARS-CoV-2 infection. UNI418 targets enzymes involved in cell membrane dynamics, essential for the virus's entry. The researchers conclude that UNI418, by blocking PIP5K1C and PIKfyve, offers a promising approach to preventing SARS-CoV-2 infection and emphasizes the importance of targeting the virus's entry process as a treatment strategy. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
- Publication
Experimental & Molecular Medicine EMM, 2024, Vol 56, Issue 8, p1736
- ISSN
1226-3613
- Publication type
Article
- DOI
10.1038/s12276-024-01283-2