Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

作     者：Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan 

作者机构：Department of Medicinal ChemistryKey Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen Research Institute of Shandong UniversityShenzhen 518057China The Key Laboratory of Infection and Immunity of Shandong ProvinceDepartment of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a Molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous University of Madrid)Madrid 28049Spain KU LeuvenDepartment of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第1期

页      面：87-109页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 081702[工学-化学工艺] 08[工学] 0817[工学-化学工程与技术] 

基　　金：We gratefully acknowledge financial support from Major Basic Research Project of Shandong Provincial Natural Science Foundation(ZR2021ZD17,China) Science Foundation for Outstanding Young Scholars of Shandong Province(ZR2020JQ31,China) Foreign Cultural and Educational Experts Project(GXL20200015001,China) Guangdong Basic and Applied Basic Research Foundation(2021A1515110740,China) China Postdoctoral Science Foundation(2021M702003) This work was supported in part by the Ministry of Science and Innovation of Spain through grant PID2019-104176RBI00/AEI/10.13039/501100011033 awarded to Luis Menéndez-Arias An institutional grant of the Fundación Ramón Areces(Madrid,Spain)to the CBMSO is also acknowledged.Luis Menéndez-Arias is member of the Global Virus Network 

主　　题：COVID-19 SARS-CoV-2 Main protease Non-covalent inhibitors Medicinal chemistry strategies 

摘      要：The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life *** covalent M^(pro)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 *** antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable *** non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available *** viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.