Year: 2023
Type: article
Abstract: Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing drugs against COVID-19.Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP and RNA-IP were used to confirm the regulation of HuR on mRNA of CD147. Regulation of niclosamide on HuR nucleo-translocation was assessed by immunofluorescence staining of cell lines, IHC staining of tissue of mouse model and western blotting. Finally, the suppression of niclosamide on SARS-CoV-2 infection induced CD147 was evaluated by ACE2-expressing A549 cells and western blotting.Results We first discovered a novel regulation mechanism of CD147 via the RNA-binding protein HuR. We found that HuR regulates CD147 post-transcription by directly bound to its 3'-UTR. The loss of HuR reduced CD147 in multiple cell lines. Niclosamide inhibited CD147 function by blocking HuR cytoplasmic translocation and diminishing CD147 glycosylation. SARS-CoV-2 infection induced CD147 in ACE2-expressing A549 cells, which could be neutralized by niclosamide in a dose-dependent manner.Conclusion Together, our study reveals a novel regulation mechanism of CD147 and niclosamide can be repurposed as an effective COVID-19 drug by targeting the virus entry, CD147-spike protein.
Source: Biomedicines
Authors: Zhe Yang, Qi Zhang, Xiaoqing Wu, Siyuan Hao, Xinbao Hao, Elizabeth Jones, Yuxia Zhang, Jianming Qiu, Liang Xu
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,447
Funders: U.S. Department of Defense, Kansas Bioscience Authority, National Institutes of Health, Centers for Disease Control and Prevention, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, DOD Prostate Cancer Research Program
Awards: G1261483950, G1673673948, G1679715603, Integrative Functional Profiling of Tumor-Derived Extracellular Vesicles, G3535678918, G5017364282, G5164223474, G5238863915, G5432260050, G5597503317, G6047482813, G6688086235, G6921509183, G7793961685, Novel therapeutic strategy for renal fibrosis by targeting RNA-binding protein HuR, G9000014190, G9000027165, G9000164315, G9000205454, G9000247235, G9000290181
OpenAlex ID: W4384828445