Rothan, Hussin A. and Teoh, Teow Chong (2021) Cell-based high-throughput screening protocol for discovering antiviral inhibitors against SARS-COV-2 main protease (3CLpro). Molecular Biotechnology, 63 (3). pp. 240-248. ISSN 1073-6085, DOI https://doi.org/10.1007/s12033-021-00299-7.
Full text not available from this repository.Abstract
The global public health has been compromised since the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in late December 2019. There are no specific antiviral drugs available to combat SARS-CoV-2 infection. Besides the rapid dissemination of SARS-CoV-2, several variants have been identified with a potential epidemiologic and pathogenic variation. This fact has forced antiviral drug development strategies to stay innovative, including new drug discovery protocols, combining drugs, and establishing new drug classes. Thus, developing novel screening methods and direct-targeting viral enzymes could be an attractive strategy to combat SARS-CoV-2 infection. In this study, we designed, optimized, and validated a cell-based assay protocol for high-throughput screening (HTS) antiviral drug inhibitors against main viral protease (3CLpro). We applied the split-GFP complementation to develop GFP-split-3CLpro HTS system. The system consists of GFP-based reporters that become fluorescent upon cleavage by SARS-CoV-2 protease 3CLpro. We generated a stable GFP-split-3CLpro HTS system valid to screen large drug libraries for inhibitors to SARS-CoV-2 main protease in the bio-safety level 2 laboratory, providing real-time antiviral activity of the tested compounds. Using this assay, we identified a new class of viral protease inhibitors derived from quinazoline compounds that worth further in vitro and in vivo validation.
| Item Type: | Article |
|---|---|
| Funders: | Institut Pengurusan dan Pemantauan Penyelidikan, University of Malaya, TRGS Grant (TR001B-2014B) |
| Uncontrolled Keywords: | SARS-CoV-2; Protease; GFP complementation; High-throughput screening; Drug libraries |
| Subjects: | Q Science > QR Microbiology R Medicine |
| Divisions: | Faculty of Science |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 10 Mar 2022 04:34 |
| Last Modified: | 10 Mar 2022 04:35 |
| URI: | http://eprints.um.edu.my/id/eprint/27560 |
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