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。     

瑞德西韦对冠状病毒抑制作用的研究进展

冠状病毒(CoV)作为人畜共患病毒,轻可致人出现轻度呼吸道感染症状,重可致高传播性和严重肺部感染等,例如严重急性呼吸综合征冠状病毒(SARS-CoV)与中东呼吸综合征冠状病毒(MERS-CoV).2019年底新出现的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)标志着高致病性冠状病毒在全球的再次流行,目前这种新冠状病毒肺炎被WHO命名为COVID-19.而新型核苷酸类似物抗病毒药瑞德西韦(Remdesivir;GS-5734)作为一种广谱抗病毒药物,对SARS-CoV与MERS-CoV表现出一定的抗病毒活性.本文综述冠状病毒的起源与发展、种类、结构及对人类健康的影响,并针对瑞德西韦的分子结构特点、抗病毒的特点及其治疗人冠状病毒感染的国内外新进展做一系统总结,以期为抗冠状病毒的药物选择提供参考.     

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     

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．     

冠状病毒感染过程中血管紧张素转换酶2作用的研究进展

冠状病毒可引起人类呼吸道、肠道等多系统感染.严重急性呼吸综合征冠状病毒(SARS-CoV,2003年)、人冠状病毒NL63(HCoV-NL63,2004年)以及目前的新型冠状病毒(SARS-CoV-2,2019年)均已被证实通过与黏膜的血管紧张素转换酶2(ACE2)结合感染人体.因此研究冠状病毒感染过程中ACE2的作用有助于了解冠状病毒的致病机制,为新型冠状病毒肺炎的防治提供参考.该文综述了ACE2在3种冠状病毒感染人体过程中作用的研究进展,主要涉及病毒棘突蛋白识别ACE2胞外域顶端,且有跨膜蛋白酶丝氨酸2(TMPRSS2)等因子参与其中.针对冠状病毒与ACE2结合的机制,可以从多个靶点设计防治药物.     

封面图片说明：新型冠状病毒

 冠状病毒可分为α、β、γ、δ4个属，与人类疾病相关的冠状病毒均为α和β属冠状病毒。可知可造成人类疾病的冠状病毒有：普通人类冠状病毒229E、NL63、OC43、HKU1，严重急性呼吸综合征冠状病毒（severe acute respiratory syndrome coronavirus，SARS-CoV），中东呼吸综合征冠状病毒（Middle East respiratory syndrome coronavirus，MERS-CoV），以及2019新型冠状病毒（2019 novel coronavirus，2019-nCoV）。     

全球冠状病毒科研态势及研究热点分析

 2019年12月以来，一种新型冠状病毒感染引起的急性呼吸道传染病蔓延全球。新型冠状病毒是目前已知的第7种可以感染人的冠状病毒，20世纪以来已知的另外2种可以引起比较严重人类疾病的冠状病毒为2003年爆发的严重急性呼吸综合征冠状病毒和2012年的中东呼吸综合征冠状病毒。自冠状病毒发现以来，国内外学者针对冠状病毒已进行了大量研究，本文基于文献计量、内容分析等方法，对全球冠状病毒的研究态势进行揭示，并对冠状病毒的研究热点及研究趋势进行分析。     

新型冠状病毒

正新冠状病毒可分为α、β、γ、δ4个属,与人类疾病相关的冠状病毒均为α和β属冠状病毒。已知可造成人类疾病的冠状病毒有:普通人类冠状病毒229E、NL63、OC43、HKU1,严重急性呼吸综合征冠状病、(severe acute respiratory syndrome coronavirus,SARS-CoV),中东呼吸综合征冠状病毒(Middle     

SARS病毒与SARS疫苗

今年4月16日世界卫生组织正式公布SARS-CoV为造成“非典”或严重急性呼吸综合症的病原。在此前后的两周之内,世界上多个实验室相继公布了这一病毒的基因序列,让我们对这一病毒有了更深入的了解。     

SARS及其它冠状病毒基因组组织结构和序列的初步比较分析

严重急性呼吸综合症(Severeacuterespiratorysydrome,SARS)是一种全新的传染性疾病,它可能主要是由冠状病毒的一个变种引起的.本文比较SARS及其它冠状病毒基因组组织结构和序列变异的情况,初步的结果表明:①尽管SARS病毒与冠状病毒属的另外6种病毒基因组序列上有较大的差异,但是它们具有较相似的基因组组织结构;②SARS病毒与牛冠状病毒、鼠肝炎病毒具有较近的系统发育关系;③虽然SARS病毒扩散的时间极短,但来自不同地区SARS病毒的DNA序列却存在一些突变,且这些突变又大多是改变氨基酸序列的非同义突变.     

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.     

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.     

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.     

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.     

Dissection of SARS Coronavirus Spike Protein into Discrete Folded Fragments

Introduction Severe acute respiratory syndrome coronavirus (SARS-CoV), which is the causative agent of the atypical pneumonia, was first identified in the fall of 2002 to be a previously unknown member of the family of coronaviruses[1]. The rapid transmis…     

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.     

传染性非典型肺炎病毒核蛋白的表达与活性检测

用PCR方法，人工合成传染性非典型肺炎病毒(SARS-CoV)核蛋白(N)全编码基因，并构建原核表达载体．在大肠杆菌中进行表达．结果重组N蛋白表达产量占菌体总蛋白的40％以上，主要以可溶形式存在．用SARS患者急性期血清进行蛋白印迹检测，表明可溶形式和包含体形式均有明显活性．包含体形式的重组蛋白经纯化后纯度可达90％以上，活性与纯化前相当，可作为SARS抗体诊断试剂盒的抗原原料．     

天然产物活性化合物抗SARS-CoV研究

针对系统综合征冠状病毒 2 (SARS-CoV-2),在全球范围大流行并呈指数级传播,迫切需要有 效的抗病毒药物和疫苗来控制和预防 SARS-CoV-2 疫情,寻找与开发有效、价格低廉的治疗 SARS-CoV-2 药物,是全世界面临的挑战;结合国内外最新文献,介绍了冠状病毒的起源、种类、人类感染的危害与应对措 施,发现药用植物与其它天然产物,其活性化合物抗 SARS-CoV 和增强免疫力廉价、可行,中医临床也证实 天然药物治疗 SARS-CoV 的有效性;天然产物包括药用植物、真菌和海洋生物的活性成分,可能成为 SARS- CoV-2 抑制剂研究与开发的新前沿。     

Spike protein homology between the SARS-associated virus and murine hepatitis virus implies existence of a putative receptor-binding region

Coronavirus has been determined to be the cause of the recent outbreak of severe acute respiratory syndrome (SARS). Human coronavirus 229E had been studied well and its receptor-binding domain was restricted to aa417-547 of S protein. However, this region has no homology with the newly separated SARS-associated virus (Hong Kong isolate CUHK-W1). Then we analyzed the phyiogenesis of S1 subunit of the coronavirus spike protein (SARS-associatedvirus, Hong Kong isolate CUHK-W1). Interestingly, thehighest homology between murine hepatitis virus (MHV)and SARS-associated coronavirus was found. And the important sites (aa62-65 and aa214-216) on the spike proteinof MHV with receptor-binding capacity were highly conservative in comparison with the newly separated SARS-associated virus (the corresponding sites are aa51-54 and aa195-197). These results from bioinformatics analysis mighthelp us to study the receptor-binding sites of SARS-associated virus and the mechanism of the virus entry into the target cell, and design antiviral drugs and potent vaccines.     

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…