期刊
BIOORGANIC CHEMISTRY
卷 129, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.106185
关键词
SARS-CoV-2; Mpro inhibitor; Acriflavine; Proflavine hemisulfate
资金
- National Natural Science Foundation of China (NSFC)
- Chunhui Program-Cooperative Research Project of the Ministry of Education, Liaoning Province Natural Science Foundation
- Shenyang Young and Middle-aged Innovative Talents Support Program
- National Key Research and Development Program of China
- Shanghai Science and Technology Committee (STCSM) Science and Technology Innovation Program
- [82141216]
- [2020-MZLH-31]
- [RC210446]
- [2021YFC2300703]
- [21S11902600]
This study discovered Acriflavine and Proflavine Hemisulfate as inhibitors of Mpro, showing good inhibitory activity against the SARS-CoV-2 virus.
The evolving SARS-CoV-2 epidemic buffets the world, and the concerted efforts are needed to explore effective drugs. Mpro is an intriguing antiviral target for interfering with viral RNA replication and transcription. In order to get potential anti-SARS-CoV-2 agents, we established an enzymatic assay using a fluorogenic substrate to screen the inhibitors of Mpro. Fortunately, Acriflavine (ACF) and Proflavine Hemisulfate (PRF) with the same acridine scaffold were picked out for their good inhibitory activity against Mpro with IC50 of 5.60 +/- 0.29 mu M and 2.07 +/- 0.01 mu M, respectively. Further evaluation of MST assay and enzymatic kinetics experiment in vitro showed that they had a certain affinity to SARS-CoV-2 Mpro and were both non-competitive inhibitors. In addition, they inhibited about 90 % HCoV-OC43 replication in BHK-21 cells at 1 mu M. Both compounds showed nano-molar activities against SARS-CoV-2 virus, which were superior to GC376 for anti-HCoV-43, and equivalent to the standard molecule remdesivir. Our study demonstrated that ACF and PRF were inhibitors of Mpro, and ACF has been previously reported as a PLpro inhibitor. Taken together, ACF and PRF might be dual-targeted inhibitors to provide protection against infections of coronaviruses.
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