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.
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).
