摘要
从今年3月起,WHO不再将新冠病毒感染,列为全球关注的灾害性卫生事件,但是新感染病例依然存在,其原因与病毒基因组经常突变,引起特异抗体失效和免疫逃逸有关,同时特异性治疗药物依然有限。病毒S蛋白是病毒感染宿主细胞的关键结构,S蛋白质突变,导致其结构生化特征和功能等随之变化。我们曾分析了世卫组织(WHO)认定的野生型和5种关切变异毒株的生化特征,并研究证实了日本刺沙蚕碱性丝氨酸蛋白酶(ASP_(NJ))可以高效与相对特异地降解野生型病毒S蛋白。本文分析了Omicron变异毒株(BA.2、BF.7、XBB.1)S蛋白质与ASP_(NJ)相关的生物化学特征,并经SDS-PAGE分析,直观证实了ASP_(NJ)可以高效降解这些S蛋白质,但变异株S蛋白抵抗ASP_(NJ)消化能力更强一些。本文还报告了ASP_(NJ)对野生型假病毒的影响,初步结果显示,ASP_(NJ)可能具有减少野生型假病毒感染293T-CAE2受体细胞的作用。这些结果表明,ASP_(NJ)有可能成为一种新工具酶,用于研究新冠病毒的结构与功能。
Since March this year,the World Health Organization no longer classified severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)as a catastrophic health event of global concern.But the number of new infections is still increasing,which is due to the failure of specific antibodies and immune escape caused by frequent mutations in the virus gene.At present,specific therapeutic drugs are still limited and lack broad spectrum.The viral S protein is the key to viral infection in human cells.Herein we show that alkaline serine protease from Neanthes japonica,pI 4.4(ASP_(NJ))could efficiently degrade the S protein of omicron variant strains BA.2,BF.7 and XBB.1,whereas the mutation S proteins obtained stronger resistance to ASP_(NJ) digestion.Preliminary experiments showed that ASP_(NJ) may reduce the pseudovirus infection into 293T-ACE2.ASP_(NJ) can widely and efficiently degrade the S protein.Thus,our results suggested that ASP_(NJ) may become a new tool enzyme for studying the structure and function of SARS-CoV-2.
作者
阚慕洁
白若伦
刘智奇
白宇
王少华
刘剑凯
洪敏
KAN Mu-Jie;BAI Ruo-Lun;LIU Zhi-Qi;BAI Yu;WANG Shao-Hua;LIU Jian-Kai;HONG Min(Biochemistry Department,College of Basic Medical Sciences,Jilin University,Changchun 130021,China;Hebei Building Materials Vocational and Technical College Hospital,Qinhuangdao 066006,Hebei,China;Shenyang Keqi Pharmaceutical Technology Development Co.,LTD,Shenyang 110000,China;Institute of Virology and AIDS Research,The First Hospital of Jilin University,Jilin University,Changchun 130021,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第2期251-257,共7页
Chinese Journal of Biochemistry and Molecular Biology
基金
吉林省卫生健康技术创新项目(No.2019J012)资助。
关键词
新冠病毒
刺突蛋白
沙蚕碱性丝氨酸蛋白酶
变异新冠病毒
假病毒
SARS-CoV-2
spike protein(S)
alkaline serine protease from Neanthes japonica(ASP NJ)
SARS-CoV-2 mutation
pseudovirus
