乙型肝炎病毒感染机制和药物治疗的研究进展

Research progress on the mechanism of hepatitis B virus infection and drug therapy

乙型肝炎病毒感染成为全球疾病负担重要原因之一,目前仍缺乏彻底根治的方法。近年来,各类研究分别从抗病毒治疗和增强宿主免疫应答两方面进行药物设计,使得乙型肝炎病毒感染治疗领域快速发展。通过梳理相关文献,本文较为系统、全面地探讨了乙型肝炎病毒的感染机制和药物治疗进展。本文表明,在抗病毒治疗过程中,核苷(酸)类似物、核衣壳组装调节剂、HBx蛋白抑制剂、核糖核酸酶H抑制剂、NTCP相关抑制剂、HBsAg释放抑制剂等药物的设计与病毒生命周期的潜在靶点环环相扣,治疗关键在于彻底清除共价闭合环状DNA病毒源库;在增强宿主免疫应答过程中,通过包括免疫检查点抑制剂、Toll样受体激动剂和干扰素制剂修复和增强患者受损的免疫应答机制,实现抑制病毒复制的治疗目标。总之,乙肝病毒感染的药物治疗之路不断向前发展中。本文以期能够为该领域的研究提供一定思路。

Hepatitis B virus infection has become one of the important causes of the global disease burden,and there is still a lack of radical treatment.In recent years,various studies have conducted drug design from the perspectives of antiviral therapy and enhancing host immune response,which have led to rapid development in the field of treatment of hepatitis B virus infection.By reviewing relevant literatures,this article systematically and comprehensively explored the infection mechanism and drug treatment progress of hepatitis B virus.This article indicated that in the process of antiviral therapy,the design of drugs including nucleos(t)ide analogues,capsid assembly modulators,HBx protein inhibitor,Ribonuclease H inhibitor,NTCP-related inhibitors and HBsAg release inhibitors is closely related to the potential targets of the virus life cycle,and the key to treatment lies in the complete elimination of the covalent closed circular DNA virus source library.In the process of enhancing the host immune response,the therapeutic goal of inhibiting virus replication is achieved by repairing and enhancing the damaged immune response mechanism of patients,including immune checkpoint inhibitors,Toll-like receptor agonists,and interferon preparations.In a word,the drug treatment of hepatitis B virus infection is developing continuously.This article aimed to provide some ideas for research in this field.