Protein Subcellular Localization Prediction and Genomic Polymorphism Analysis of the SARS Coronavirus

Introduction In March 2003, a novel coronavirus (CoV) was dis-covered in association with the outbreak of severe acute respiratory syndrome (SARS)[1-3]. The complete genome sequence of several SARS-CoV isolates was soon determined and characterized[4,5]. Comparison of variant SARS-CoV genome sequences has identified certain genetic signatures that can be used to trace sources of infection[6]. Vaccines are now being devel-oped and molecular modeling has suggested that modi-fied rhinovir…     

Bioinformatical study on the proteomics and evolution of SARS-CoV

A novel coronavirus has been identified as the causative agent of the severe acute respiratory syndrome (SARS). For all the SARS-CoV associated proteins derivated from the SARS-CoV genome, the physiochemical properties such as the molecular weight, isoelectric point and extinction coefficient of each protein were calculated. The transmembrane segments and subeellular localization (SubLoeation) prediction and conserved protein motifs search against database were employed to analyze the function of SARS-CoV proteins. Also, the homology protein sequence alignment and evolutionary distance matrix calculation between SARS-CoV associated proteins and the corresponding proteins of other coronaviruses were employed to identify the classification and phylogenetic relationship between SARS-CoV and other coronaviruses. The results showed that SARS-CoV is a novel coronavirus which is different from any of the three previously known groups of coronviruses, but it is closer to BoCoV and MHV than to other coronaviruses. This study is in aid of experimental determination of SARS-CoV proteomics and the development of antiviral vaccine.     

Molecular phylogeny of coronaviruses including human SARS-CoV

The outbreak of SARS sets an urgent task to reveal the origin of human SARS-CoV, i.e. its relation to other known species of coronavirus, and to trace the genetic variation in the spreading process of SARS. Partial answer to the problem may be obtained from phylogenetic analy-sis of available genomes. We call a phylogenetic tree of different species of coronavirus including the human SARS-Cov a CoV Tree and that of different isolates of SARS-CoV a SARS Tree. CoV trees have been c…     

冠状病毒主蛋白酶及其化学抑制剂研究进展

一个新的冠状病毒已经被鉴定为急性呼吸道综合症(SARS)的病原体,控制该病毒复制复合体活性的主蛋白酶(Mpro或3CLpro)将很可能成为开发针对SARS特效治疗药物的靶位点.综述了人冠状病毒株229E(HCoV 229E)和一种在猪体内引发传染性胃肠炎的病毒(TGEV)的Mpro的晶体结构以及以此为基础构建的SARS冠状病毒(SARS-CoV)同源蛋白酶的空间结构模型.通过对这些同源蛋白酶的结构及其与已知的蛋白酶化学抑制剂的结合特征进行分析后发现Mpro的底物结合位点具有惊人的保守性,这种保守性也被重组SARS-CoV Mpro能介导的TGEV Mpro的底物剪切实验所进一步证实.分子模型表明已有的鼻病毒3Cpro抑制剂经过改进后或许能用于SARS的治疗.     

SARS的研究进展

2003年3月,发现SARS病原是一种从未在人类或动物中发现过的新的冠状病毒.其基因组结构与其他的冠状病毒相似,由29727核苷酸组成,有11个开放阅读框.通过多基因分析序列比较说明,SARS冠状病毒与已知的冠状病毒无关.针对SARS冠状病毒的各种特征及研究进展进行了综述.     

SARS相关冠状病毒刺突糖蛋白的研究(综述)

概述了SARS—CoV的S蛋白的结构及功能相关研究。严重急性呼吸综合症相关的冠状病毒(SARS-CoV)引起2003年我国南方非典型肺炎爆发流行，波及多个国家和地区。目前全球许多学对SARS-CoV进行了广泛的研究，发现S蛋白是病毒表面的主要蛋白，它构成冠状病毒科特征性的冠状样结构，在严重急性呼吸综合症的发病机制起着关键性作用，可介导表达相关受体的宿主细胞感染。现已鉴定出SARS-CoV的S蛋白相关受体，同时它在抗病毒感染中是一个关键靶蛋白。     

基于密码子使用模式的冠状病毒亲缘关系分析

重症急性呼吸综合症(severe acute respiratorysyndrome,SARS),临床表现为非典型肺炎.由于SARS具有很高的传染性和一种新型的冠状病毒(SARS-CoV)被认为是引起SARS的病原体.SARS冠状病毒(SARS-CoV)属于巢状病毒目(OrderN idovirales),冠状病毒科(Fam ily Coronaviri-dae),冠状病     

Preparation, characterizationand preliminary in vivo studies of inactivated SARS-CoV vaccine

A large quantity of SARS-CoV virus was proliferated in Veto cells, inactivated with β-ptopiolactone, then purified by Sepharose 4FF column chromatography to prepare inactivated vaccine. The vaccine was identified by Western blot, mass spectrographic analysis, ELISA and electton microscopy. The vaccine with or without aluminum hydtoxide adjuvant was inoculated into female BALB/c mice at different dosages. The result showed that the antibodies to SARS-CoV were induced in the mice. The antibody levels induced by the vaccine with aluminum hydroxide were higher than those without aluminum hydroxide.     

A Coordination Model of Gene Sequences for SARS-CoV and its Receptor

IntroductionFrom the emergence of SARS CoV, manystudies havebeen done on its biological medicine aspects, such aspathogeny characteristics, mechanisms of causing disease,clinic diagnosis and treatment, bacterin development andthe spreading rules. At the level of molecule biology,studies have been done on its genome sequences characteristics, structures and functions of the translatedproteins, and the evolution relationships in sequences[1 5].The caus…     

SARS-CoVS基因表达及纯化

严重急性呼吸道综合症是由一种新的冠状病毒SARS-CoY引起的．作者通过PCR扩增得到了S蛋白的6个编码片段，并利用表达载体pET28a( )在E．coli BL21中进行了原核表达．通过亲和层析纯化了包含大部分ACE2结合区域的S蛋白片段(S4)．ELISA分析结果表明S4与SARS病人恢复期血清具有良好的反应能力．     

SARS冠状病毒及相关病毒的分子系统学分析

根据SARS冠状病毒及其相关病毒的基因组核酸序列和3种不同蛋白质序列，应用最大简约法和最小进化法重建系统发育树；并对SARS冠状病毒的11个推测蛋白质(ORF)做BLAST分析。结果表明，SARS冠状病毒和鼠肝炎病毒——牛冠状病毒分支构成姊妹群。其单系群性质得到强有力的统计学支持。这暗示了SARS的爆发可能源自种间屏障的突破事件，该病毒天然宿主可能为猪、牛或鼠。SARS冠状病毒与已知的人冠状病毒分属冠状病毒科的不同分支，因此致病机制可能有很大不同。3个基因的系统树分支格局的一致性表明：SARS冠状病毒这3个主要基因与其他冠状病毒间不存在重组，但全部11个ORF的BLAST分析却认为其基因组上一些小的区段可能与其他病毒存在重组。     

SARS冠状病毒的诊断性实验研究

严重急性呼吸综合征(SARS)是一种新的人类感染性疾病，其致病菌为SARS冠状病毒(SARS-CoV)。本文就SARS-CoV发现过程、病毒特点及检测方法的研究进展和应用情况加以概述。     

Phylogeny of SARS-CoV as inferred from complete genome comparison

SARS-CoV, as the pathogeny of severe acute respi-ratory syndrome (SARS), seems to be the first coronavirus that is lethal to humans. Coronavirus (family Coronaviri-dae, genus Coronavirus) is an enveloped, single-stranded plus sense RNA virus whose genome has approximately 30 kb size. Whereas coronaviruses may cause severe dis-ease in animals, coronaviruses human strains only cause mild diseases until SARS-CoV was discovered. To date, SARS-CoV genomes from 12 isolates have been comp…     

A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model.     

引起人非典型性肺炎的冠状病毒基因组与其它冠状病毒基因组的初步比较

一种在世界范围内突然爆发的致命流行病——急性呼吸窘迫综合症(SARS)击倒了数干人，一种全新的冠状病毒被认为是其病原．5个SARS相关冠状病毒的全基因组序列已经完成．我们进行了SARS相关冠状病毒和其它冠状病毒的基因组进化分析和序列比较，结果显示：1．SARS相关冠状病毒不直接来自于任何已知的冠状病毒；2．E蛋白的基因可能是在近期从其它病毒横向转移到SARS病毒中来的；3．Sl和S2基因发生了较大范围的缺失或插入突变．这些基因横向转移和突变改变了SARS相关病毒的表面结构和抗原性，极有可能是导致其获得侵染人类细胞的主要原因．     

对SARS制定科学术语的意见

建议将现称的萨斯(SARS)改称传染性冠状病毒肺炎。     

SARS冠状病毒基因组复制酶起始结合位点的预测

严重急性呼吸综合征(Severe Acute Respiratory Syndrome，SARS)传染性强，死亡率高，给全世界约30个国家造成了巨大损失．其病原体为SARS冠状病毒(Severe acute Respiratory Syndrome Associated Coronavirus，SARS—CoV)，是冠状病毒(Coronavirus)的新变异种．作者以“最大信息量”理论和方法为基础，使用结合位点搜寻软件等生物信息学方法，对冠状病毒基因组的3’非翻译区(Untranslated Regions，UTRs)进行分析，预测出了2株SARS—CoV(来自北京的SARSBJ01和浙江的SARSZJ01)以及其他38株冠状病毒株的复制酶起始结合位点(Replicase initial binding sites，RIBS)．在该预测结果中，不难发现，这些RIBS的序列与前人的研究成果有很大的相似之处，与公认的冠状病毒的顺式作用元件极为相似的基序也存在其中，而且其预测的二级结构与鼠肝炎病毒MHV基因组的某些蛋白结合位点类似．因此，预测的RIBS在病毒的复制中可能起重要作用．     

2020年新型冠状病毒分子病理学研究及其药物和疫苗研发热点回眸

 新型冠状病毒于2019年12月被发现以来，引发了严重的呼吸系统传染病疫情，并波及世界所有主要国家和地区。全球科学界迅速行动起来，对该病毒及其引发的疾病进行了广泛而深入的研究。得益于此前在严重急性呼吸道综合征冠状病毒和中东呼吸综合征冠状病毒上的知识积累，针对新型冠状病毒的科研工作在2020年取得了丰硕的研究成果，特别是在分子病理学方面获得了很多透彻的认知，这些知识的获得又为针对新型冠状病毒的药物和疫苗研发奠定了基础。简要回顾了冠状病毒的研究历史，重点总结了新型冠状病毒的分子病理学研究要点，在药物研发方面兼顾现有药物的重定位和新型抗病毒药物的研发现状，在疫苗研发方面按类型总结各国目前比较成功的疫苗项目及其研发进展。     

SARS冠状病毒的起源和进化初探

发展了一种研究基因序列进化的随机替代模型,根据一组从某个最近共同祖先演化而来的若干序列,可以预测此共同祖先序列,并计算随机替代概率矩阵,确定了从祖先序列的各个碱基到进化序列的各个碱基之间的替代概率。将这一模型应用于分析包括SARS冠状病毒在内的4种冠状病毒全基因组的演化规律,确定了在若干较保守的编码蛋白基因序列中同义替代位点的最近共同祖先序列以及分歧进化后的累计同义替代数目。结果表明,SARS病毒和其他几种已知的冠状病毒具有相当的进化历程,但存在不同的进化途径,支持了SARS病毒在造成此次大规模感染人体之前已经历了较长的进化历程的猜测。     

SARS冠状病毒核衣壳蛋白cDNA的克隆和原核表达载体的构建

目的克隆SARS冠状病毒核衣壳(N)蛋白.方法用RT-PCR技术克隆SARS冠状病毒N蛋白全长cDNA,cDNA经序列分析鉴定后,克隆到pET30a表达载体.结果实现了SARS冠状病毒N蛋白基因的克隆.结论可以对重组成功的pET30a-N进行进一步的应用.