分类: 医学、药学 >> 药学 提交时间: 2020-02-23
摘要: A novel coronavirus (SARS-CoV-2) infectious disease has broken out in Wuhan, Hubei Province since December 2019, and spread rapidly from Wuhan to other areas, which has been listed as an international concerning public health emergency. We compared the Spike proteins from four sources, SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that the SARS-CoV-2 virus sequence had redundant PRRA sequences. Through a series of analyses, we propose the reason why SARS-CoV-2is more infectious than other coronaviruses. And through structure based virtual ligand screening, we foundpotentialfurin inhibitors, which might be used in the treatment of new coronary pneumonia.
分类: 生物学 >> 病毒学 提交时间: 2020-03-06
摘要: 冠状病毒SARS-CoV,MERS-CoV和新发现的2019-nCoV所引发的传染性疾病严重威胁着人类的生命健康安全。位于冠状病毒表面的spike(S)糖蛋白在病毒传播及感染过程中负责结合宿主细胞受体,融合细胞中的膜结构等关键步骤,是病毒重要的药物靶点。其中在冠状病毒中高度保守的S2亚基作为融膜机器,介导了病毒与宿主之间的膜融合过程。我们运用冷冻电镜单颗粒三维重构技术解析了SARS-CoV S糖蛋白的融膜后构象的结构,展示了S2亚基在融膜过程中的结构特点和构象变化。结合保守性比对和糖基化修饰指认,这项工作分析了位于S2亚基的潜在药物靶点,有益于相关疫苗和药物的开发和设计。
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: We recently described the discovery, genome, clinical features, genotypes and evolution of a novel and global human respiratory virus named human coronavirus HKU1 (HCoV-HKU1) which is not yet culturable. We expressed a C-terminal FLAG-tagged CoV-HKU1 spike (S) protein by the Semliki Forest Virus (SFV) system and investigated its maturation profile. Pulse chase labeling revealed that S-FLAG was expressed as high-mannose N-glycans of monomers and trimers. It was predominantly cleaved into subdomains S1 and S2 during maturation. S1 was secreted into the medium. Immunofluorescence analysis visualized S along the secretory pathway from endoplasmic reticulum to plasma membrane. Cleavage of S and release of HCoV-HKU1 S pseudotyped virus were inhibited by furin or furin-like enzyme inhibitors. The cell-based expressed full-length S-FLAG could be recognized by the convalescent serum obtained from a patient with HCoV-HKU1 pneumonia. The data suggest that the native form of HCoV-HKU1 spike expressed in our system can be used in developing serological diagnostic assay and in understanding the role of S in the viral life cycle. Exp Biol Med 233:1527-1536, 2008