摘要
新型冠状病毒(Severe acute respiratory syndromes coronavirus 2, SARS-CoV-2)引发的新型冠状病毒肺炎(Coronavirus disease 2019, COVID-19)疫情对全球公众健康造成了巨大危害,能有效防治COVID-19的抗病毒药物仍在探索中。核衣壳(Nucleocapsid, N)蛋白是SARS-CoV-2的关键结构蛋白,通过与病毒基因组RNA和其他结构蛋白结合后组装成病毒颗粒,保护病毒基因组进而促进病毒复制和传播。此外,N蛋白还作为调节蛋白在维持病毒生命周期以及干扰宿主天然免疫反应和应激颗粒组装等方面发挥重要作用。因此,靶向N蛋白的抗病毒策略近年来受到了SARS-CoV-2抗病毒药物研究的广泛关注,如靶向N蛋白的RNA结合域、翻译后修饰以及液相分离等。此外,N蛋白在不同SARS-CoV-2变异株中突变率低,其结构和功能在多种感染人的冠状病毒中也相对保守。因此,靶向SARS-CoV-2 N蛋白的抗病毒药物可能对多种人冠状病毒及其变异株均能发挥作用。本文主要就近年来靶向SARS-CoV-2 N蛋白抗病毒药物的研究进展作一概述与探讨。
The coronavirus disease 19(COVID-19)pandemic,caused by severe acute respiratory syndromes coronavirus 2(SARS-CoV-2),has posed a significant global threat to public health.Antiviral drugs that can effectively prevent and treat COVID-19 are still under active investigation.The nucleocapsid(N)protein is a key structural protein of SARS-CoV-2 that plays an essential role in viral replication and transmission.By binding to the viral genomic RNA and other structural proteins,it helps assemble viral particles and protects the viral genome.Additionally,the N protein functions as a regulatory protein,playing a crucial role in maintaining the viral life cycle,as well as interfering with the host's innate immune response and the assembly of stress granules.Consequently,antiviral strategies targeting N protein have attracted extensive attention in the development of SARS-CoV-2 antiviral drugs,such as those targeting the RNA binding domain,posttranslational modifications,and liquid-liquid phase separation of the N protein.Moreover,the N protein exhibits a low mutation rate across various SARS-CoV-2 variants and is structurally and functionally conserved among different human-infecting coronaviruses.Therefore,antiviral drugs targeting the N protein of SARS-CoV-2 may also be effective against various human coronaviruses as well as their variants.This article provides a summary and discussion of the recent research progress on antiviral drugs targeting the SARS-CoV-2 N protein.
作者
韩谢瑜
倪诗晨
蒋凯怡
邬春秀
金志刚
HAN Xieyu;NI Shichen;JIANG Kaiyi;WU Chunxiu;JIN Zhigang(College of Life Sciences,Zhejiang Normal University,Jinhua 321004,China)
出处
《病毒学报》
北大核心
2025年第3期901-914,共14页
Chinese Journal of Virology
基金
国家自然科学基金(项目号:31970755),题目:Hedgehog信号通路与应激颗粒的交互作用及其功能研究
金华市科技局重点项目(项目号:2021-3-146),题目:靶向新型冠状病毒SARS-CoV-2 N蛋白的抗病毒药物研发及应用评价
国家级大学生创新创业训练计划支持项目(项目号:202310345047),题目:基于阻断冠状病毒N蛋白与G3BP互作的抗病毒药物研究。
