Not Available.
10.1016/j.apsb.2023.08.004
- Author:
Letian SONG
1
;
Shenghua GAO
1
;
Bing YE
1
;
Mianling YANG
1
;
Yusen CHENG
1
;
Dongwei KANG
1
;
Fan YI
2
;
Jin-Peng SUN
3
;
Luis MENÉNDEZ-ARIAS
4
;
Johan NEYTS
5
;
Xinyong LIU
1
;
Peng ZHAN
1
Author Information
1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
2. The Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
3. Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
4. Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Autonomous University of Madrid), Madrid 28049, Spain.
5. KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven 3000, Belgium.
- Publication Type:Review
- From:
Acta Pharmaceutica Sinica B
2024;14(1):87-109
- CountryChina
- Language:English
-
Abstract:
The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.
