Medicinal chemistry strategies in the discovery and optimization of HBV core protein allosteric modulators(2018-2022 update)  

作　　者：Xiaoyu Shao Shujing Xu Xufeng Wan Yang Zhou Shuo Wang Shuo Wu Yuhuan Li Xinyong Liu Peng Zhan 

机构地区：[1]Department of Medicinal Chemistry,Key Laboratory of Chemical Biology,Ministry of Education,School of Pharmaceutical Sciences,Shandong University,Ji’nan 250012,China [2]CAMS Key Laboratory of Antiviral Drug Research,Beijing Key Laboratory of Antimicrobial Agents,NHC Key Laboratory of Biotechnology of Antibiotics,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2023年第11期20-30,共11页中国化学快报（英文版）

基　　金：financial support from the National Natural Science Foundation of China(NSFC Nos.82173677,82211530493);the Science Foundation for Outstanding Young Scholars of Shandong Province(No.ZR2020JQ31).

摘　　要：Despite the improving coverage of preventative vaccines,hepatitis B remains a severe global public health problem,with more than 250 million patients living with hepatitis B virus(HBV)infection.Current available therapies,including nucleos(t)ide analogs and peginterferon,can control HBV replication but fail to eliminate covalently closed circular DNA(cccDNA)and achieve a cure.The HBV core protein(Cp)is a well-conserved structural protein,self-assembling to form the viral capsid.It involves in or modulates almost every stage of the HBV lifecycle,which makes it an attractive target for the development of new anti-HBV therapies.HBV core protein allosteric modulators(CpAMs)have become a hotspot in recent years.Herein,we provide a concise report focusing on the various medicinal chemistry strategies involved in the latest research(2018-2022)of HBV CpAMs,including high throughput screening(HTS),virtual screening(VS),drug repositioning,natural products,substitution decorating approach,scaffold hopping,molecular hybridization,prodrug strategy and conformational constraint strategy,to provide guidance for further development of new and effective anti-HBV drugs.

关 键 词：HBV CAPSID CpAMs Medicinal chemistry strategies Drug design 

分 类 号：R51[医药卫生—内科学]