Academic Journal
Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease
| العنوان: | Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease |
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| المؤلفون: | Kai S. Yang, Syuan-Ting Alex Kuo, Lauren R. Blankenship, Zhi Zachary Geng, Shuhua G. Li, David H. Russell, Xin Yan, Shiqing Xu, Wenshe Ray Liu |
| المصدر: | Current Research in Chemical Biology, Vol 2, Iss , Pp 100025- (2022) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Biochemistry, QD415-436 |
| الوصف: | The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (MPro), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with MPro. The in vitro potency test shows that halicin inhibits the activity of MPro an IC50 of 181.7 nM. Native mass spectrometry and X-ray crystallography studies clearly indicate that the nitrothiazole fragment of halicin covalently binds to the catalytic cysteine C145 of MPro. Interaction and conformational changes inside the active site of MPro suggest a favorable nucleophilic aromatic substitution reaction mechanism between MPro C145 and halicin, explaining the high inhibition potency of halicin towards MPro. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| ردمك: | 978-2-666-24692-3 2-666-24692-2 |
| تدمد: | 2666-2469 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2666246922000076; https://doaj.org/toc/2666-2469; https://doaj.org/article/8deb17e15de94646bf0913db2cbb27e0 |
| DOI: | 10.1016/j.crchbi.2022.100025 |
| الاتاحة: | https://doi.org/10.1016/j.crchbi.2022.100025 https://doaj.org/article/8deb17e15de94646bf0913db2cbb27e0 |
| رقم الانضمام: | edsbas.E9E84623 |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9782666246923 2666246922 |
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| تدمد: | 26662469 |
| DOI: | 10.1016/j.crchbi.2022.100025 |