从多角度分析SARS-CoV-2和SARS冠状病毒(SARS-CoV)差异

新型冠状病毒肺炎(COVID-19)在全球范围内持续肆虐,感染人数与日俱增.COVID-19的病毒SARS-CoV-2与2003年发生的严重急性呼吸系统综合症冠状病毒(SARS coronavirus,SARS-CoV)同属冠状病毒.本研究就COVID-19与SARS冠状病毒的差异以及两种冠状病毒的中间宿主进行分析和探...     

SARS-CoV的分子生物学研究

SARS-CoV是引起严重急性呼吸道综合症(SARS)的病原体．更多地了解SARS-CoV的基因组、蛋白结构以及它与其它冠状病毒的关系,将有助于SARS疾病的防治．     

SARS病毒与动物冠状病毒的比较

1SARS病毒横空出世 2003年4月16日世界卫生组织宣布,肆虐人类的SARS(Severe Acute Respiratory Syndrome,严重急性呼吸道综合症)即所谓非典型肺炎的病原体已经确定,它是一种全新的寇状病毒,并建议命名为SARS病毒.     

冠状病毒与SARS

最近在世界部分地区流行的非典型肺炎是病毒引起的严重急性呼吸综合征,它是由一种新的冠状病毒引起的,这种病毒被称为SARS病毒。结合SARS病毒对冠状病毒的研究现状进行了简单概括,并概述了SARS的流行特点和可能的发病机理。     

SARS病毒与动物冠状病毒的比较

1 SARS病毒横空出世 2003年4月16日世界卫生组织宣布,肆虐人类的SARS(Severe Acute Respiratory Syndrome,严重急性呼吸道综合征)即所谓非典型性肺炎的病原体已经确定,它是一种全新的冠状病毒,并建议命名为SARS病毒。得出这一结论是基于基因序列和动物试验的两个重要依据,其一,包括中国在内     

SARS病原体特征与临床实验室诊断

SARS的全球性流行带来了严重的公共卫生问题和社会经济问题。目前,在SARS病原体鉴定、基因组结构和序列变异、SARS流行特征和实验室诊断等方面获得了很大的进展。现已证实SARS的病原体为SARS冠状病毒。SARS冠状病毒是一种与原来已知冠状病毒在某些方面类似、但又独具特征的新型冠状病毒,该病毒的起源可能源于野生动物。多个SARS冠状病毒的全基因组核酸序列测定现已完成,在SARS冠状病毒的实验室诊断方面,现已有了免疫学方法检查抗体和分子生物学方法检查病毒RNA。直接检测病毒抗原和定量检测病毒多靶点基因是今后的发展方向。     

严重急性呼吸道综合征冠状病毒疫苗研究现状

冠状病毒被认为是新近爆发的严重急性呼吸道综合征的病原体.迄今公共数据库中已发表了不同国家和地区分离的12个SARS病毒株基因组完整序列.突起蛋白是冠状病毒的主要抗原,包含许多抗原决定簇.SARS冠状病毒突起蛋白的相对保守性为有效疫苗的开发奠定了很好的研究基础.灭活或减毒的冠状病毒疫苗存在一定的局限性和危险性.开展基因工程疫苗和核酸疫苗的制备研究以及相关候选疫苗的联合应用研究将是一个切实可行的途径.     

SARS冠状病毒基础研究进展

SARS(severe acute respiratory syndrome,严重急性呼吸综合症)是严重危害人类健康的传染病,现已发现其病原体为正链RNA冠状病毒(coronavirus,CoV),SARS CoV为一类新型的冠状病毒,至今没有有效对抗其感染的药物。本文从SARS CoV的功能受体、蛋白酶、疫苗和RNA干扰技术在SARS CoV研究中的应用等方面综述了其基础研究进展,旨在为抗SARS CoV的药物研制提供一定的理论依据。     

SARS病毒:非典型肺炎相关病毒

SARS是目前在世界范围内流行的严重呼吸系统疾病。SARS病毒是有包膜的正链RNA病毒,属冠状病毒科,为新近分离鉴定的该疾病相关病原体。初步预测该病毒的复制周期与其他冠状病毒类似,但其细胞膜受体结合蛋白S的S1区、M跨膜糖蛋白等部分则存在较大的变异,可能是该病毒发生宿主改变的原因之一。此外,对SARS病毒的检测、临床诊断等方面也取得了一定的进展。     

广州某医院职工SARS病毒抗体的检测

临床上有多种病原体可以引起肺炎等呼吸道疾病,较常见的有细菌、病毒、衣原体、支原体、立克次体等。一种新型冠状病毒被确认是引起传染性非典型肺炎即严重急性呼吸道综合征SARS)的病原1。广东是最早出现SARS病例的地区,而广州是发病率较高的地区,广州市某医院是收治SARS患者的重点医院,共收治了临床确诊SARS患者261例。为了解该医院职工SARS病毒的感染情况,我们对该院505例职工的血清进行了检测。1材料与方法1.1研究对象与样品收集505例研究对象均为2003年2月至6月期间在广州重点收治SARS患者的某医院的工作人员。每人抽取3ml血,…     

Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS

In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called "distorted key" approach) was also briefly elucidated.     

Orchitis: a complication of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) coronavirus has been known to damage multiple organs; however, little is known about its impact on the reproductive system. In the present study, we analyzed the pathological changes of testes from six patients who died of SARS. Results suggested that SARS caused orchitis. All SARS testes displayed widespread germ cell destruction, few or no spermatozoon in the seminiferous tubule, thickened basement membrane, and leukocyte infiltration. The numbers of CD3+ T lymphocytes and CD68+ macrophages increased significantly in the interstitial tissue compared with the control group (P < 0.05). SARS viral genomic sequences were not detected in the testes by in situ hybridization. Immunohistochemistry demonstrated abundant IgG precipitation in the seminiferous epithelium of SARS testes, indicating possible immune response as the cause for the damage. Our findings indicated that orchitis is a complication of SARS. It further suggests that the reproductive functions should be followed and evaluated in recovered male SARS patients.     

SARS相关冠状病毒及其基因组

正在全球部分地区流行的严重急性呼吸综合征(SARS),由于其传染性强、危害性大而引起了广泛关注。各国实验室密切协作,在数月时间内分离出了SARS冠状病毒(SARSCoV),测定了病毒基因组序列,并在猴体内初步再现出SARSCoV所致肺部疾病与人相似,这些工作为遏制SARS的蔓延发挥了重要作用。现就SARSCoV的鉴定、基因组及其产物的结构与功能做一综述。     

Understanding SARS with Wolfram approach

Stepping acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) as another type of disease has been threatening mankind since late last year. Many scientists worldwide are making great efforts to study the etiology of this disease with different approaches. 13 species of SARS virus have been sequenced. However, most people still largely rely on the traditional methods with some disadvantages. In this work, we used Wolfram approach to study the relationship among SARS viruses and between SARS viruses and other types of viruses, the effect of variations on the whole genome and the advantages in the analysis of SARS based on this novel approach. As a result, the similarities between SARS viruses and other coronavirusxes are not really higher than those between SARS viruses and non-coronaviruses.     

Molecular pathogenesis of severe acute respiratory syndrome

The global outbreak in 2002-2003 of severe acute respiratory syndrome (SARS) posed a serious threat to public health and had a significant impact on socioeconomic stability. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential, and up to date, no specific treatment exists for this disease. Here we review the progress of studies on the pathogenesis of the disease, in particular, studies on the molecular level.     

New infections: myths and reality

New contemporary data about new infectious diseases of XXI century are presented. Data on morbidity and mortality from severe acute respiratory syndrome (SARS, atypical pneumonia) and avian influenza are analyzed and compared with World Health Organization data on human influenza. Biologic characteristics of avian influenza virus A/H5N1 are discussed as well as possibility of its human-to-human transmission. Principles of SARS and avian influenza infections transmission as zoonoses are described as well as mechanisms of transmission impeding their ability to infect humans. It has been argued that SARS should be regarded as contagious infection, whereas avian influenza - as non-contagious. Features of all stages of epidemic process of these infections are analyzed.     

Preparedness for SARS in the UK in 2003

Severe acute respiratory syndrome (SARS) has been described as the first major emerging infectious disease of the twenty-first century. Having initially emerged, almost unnoticed, in southern China, it rapidly spread across the globe. It severely tested national public health and health systems. However, it also resulted in rapid, intensive international collaboration, led by the World Health Organization, to elucidate its characteristics and cause and to contain its spread. The UK mounted a vigorous public health response. Some particular issues concerned: the practicalities of implementing exit screening had this been required; the likely efficacy of this and other control measures; the legal base for public health action; and the surge capacity in all systems should the disease have taken hold in the UK. We have used this experience of 2003 to inform our preparation of a framework for an integrated, escalating response to a future re-emergence of SARS according to the levels of disease activity worldwide. Recent cases confirm that SARS has not "gone away". We cannot be complacent about our contingency planning.     

Cell entry mechanism of coronaviruses: implication in their pathogenesis

Coronaviruses infect many species of animals, including humans. Among them, murine coronavirus, mouse hepatitis virus (MHV) has been well studied as a model of human diseases, such as hepatitis and demyelinating disease. An agent causing severe acute respiratory disease (SARS), SARS coronavirus (SARS-CoV), is a newcomer in this genus, however, it is now one of the most studied coronaviruses due to its medical impact. The receptors of those two viruses have been identified and their cell entry mechanism has been actively investigated. Recently, SARS-CoV cell entry mechanism is shown to be different from that of other enveloped viruses, including MHV. In this review, cell entry mechanism of those two viruses is described, stressing on the difference and similarity found between those two viruses.     

The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase

The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. Accurate determination of the dimer dissociation constant and the role of the N-finger (residues 1-7) will provide more insights into the enzyme catalytic mechanism of SARS 3CL proteinase. The dimer dissociation constant of the wild-type protein was determined to be 14.0microM by analytical ultracentrifugation method. The N-finger fragment of the enzyme plays an important role in enzyme dimerization as shown in the crystal structure. Key residues in the N-finger have been studied by site-directed mutagenesis, enzyme assay, and analytical ultracentrifugation. A single mutation of M6A was found to be critical to maintain the dimer structure of the enzyme. The N-terminal octapeptide N8 and its mutants were also synthesized and tested for their potency as dimerization inhibitors. Peptide cleavage assay confirms that peptide N8 is a dimerization inhibitor with a K(i) of 2.20mM. The comparison of the inhibitory activities of N8 and its mutants indicates that the hydrophobic interaction of Met-6 and the electrostatic interaction of Arg-4 contribute most for inhibitor binding. This study describes the first example of inhibitors targeting the dimeric interface of SARS 3CL proteinase, providing a novel strategy for drug design against SARS and other coronaviruses.     

Molecular cloning, expression, purification, and mass spectrometric characterization of 3C-like protease of SARS coronavirus

Severe acute respiratory syndrome (SARS) is an acute respiratory illness, which has broken out in China. It has been known that SARS coronavirus (SARS_CoV) is a novel human coronavirus and is responsible for SARS infection. Belonging to one of the major proteins associated with SARS_CoV, SARS 3C-like protease (SARS_3CL(pro)) functions as a cysteine protease engaging in the proteolytic cleavage of the viral precursor polyprotein to a series of functional proteins required for coronavirus replication and is considered as an appealing target for designing anti-SARS agents. To facilitate the studies regarding the functions and structures of SARS_3CL(pro), in this report the synthetic genes encoding 3CL(pro) of SARS_CoV were assembled, and the plasmid was constructed using pQE30 as vector and expressed in Escherichia coli M15 cells. The highly yielded ( approximately 15mg/L) expressed protease was purified by use of NTA-Ni(2+) affinity chromatography and FPLC system, and its sequence was determined by LC/MS with the residue coverage of 46.4%.