Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2
| العنوان: | Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2 |
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| المؤلفون: | Junjiao Yang, Yinghong Xiao, Peter V. Lidsky, Chien-Ting Wu, Luke R. Bonser, Shiming Peng, Miguel A. Garcia-Knight, Michel Tassetto, Chan-I Chung, Xiaoquan Li, Tsuguhisa Nakayama, Ivan T. Lee, Jayakar V. Nayak, Khadija Ghias, Kirsten L. Hargett, Brian K. Shoichet, David J. Erle, Peter K. Jackson, Raul Andino, Xiaokun Shu |
| المصدر: | Nat Microbiol Nature microbiology, vol 8, iss 1 |
| بيانات النشر: | Springer Science and Business Media LLC, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Microbiology (medical), Immunology, Peptidyl-Dipeptidase A, Antiviral Agents, Applied Microbiology and Biotechnology, Microbiology, Article, Mice, Chlorocebus aethiops, Genetics, 2.1 Biological and endogenous factors, Humans, Animals, Aetiology, Lung, Vero Cells, SARS-CoV-2, Prevention, COVID-19, Pneumonia, Cell Biology, Infectious Diseases, Emerging Infectious Diseases, Good Health and Well Being, 5.1 Pharmaceuticals, Medical Microbiology, Pneumonia & Influenza, Angiotensin-Converting Enzyme 2, Development of treatments and therapeutic interventions, Infection |
| الوصف: | The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright fluorescence signal that requires no exogenous cofactors. Utilizing this reporter, we carried out a high-throughput screening of small-molecule libraries. We identified three natural compounds that block replication of SARS-CoV-2 in both Vero cells and human primary nasal and bronchial epithelial cells. Cell biological and biochemical experiments validated all three compounds and showed that they block the early stages of viral infection. Two of the inhibitors, bruceine A and gamabufotalin, were also found to block replication of the Delta and Omicron variants of SARS-CoV-2. Both bruceine A and gamabufotalin exhibited potent antiviral activity in K18-hACE2 and wild-type C57BL6/J mice, as evidenced by reduced viral titres in the lung and brain, and protection from alveolar and peribronchial inflammation in the lung, thereby limiting disease progression. We propose that our fluorescent assay can be applied to identify antiviral compounds with potential as therapeutic treatment for COVID-19 and other respiratory diseases. |
| وصف الملف: | application/pdf |
| تدمد: | 2058-5276 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::798e39d277c2392b2cac949a17527082 https://doi.org/10.1038/s41564-022-01288-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....798e39d277c2392b2cac949a17527082 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20585276 |
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