SARS冠状病毒S蛋白的研究进展

SARS冠状病毒S蛋白是典型的I型病毒融合蛋白,在很大程度上决定了SARS冠状病毒的组织嗜性和致病性。近年来,SARS冠状病毒S蛋白己经成为研究的热点。本文就SARS冠状病毒及其S蛋白的分子生物学特点、SAILS冠状病毒入境关系、在膜融合过程作用、基因研究、与血管紧张素转化酶2（ACE2）的相互作用、受体结合域、SARS疫苗研究中的作用等综述了近年来SARS冠状病毒S蛋白的研究进展。     

SARS临床诊断和治疗进展

已经证实重症急性呼吸综合征(SARS)是由一种新型冠状病毒-SARS相关的冠状病毒(SARS—CoV)引起的。SARS在2002年末，中国的广东省始发。截至2003年7月10日，SARS在32个国家有报道，有8437人感染，813人死亡。在中国大陆截至到2003年7月10日，SARS波及26省，有5327人感染，348人死亡。到2003年7月底，北     

SARS冠状病毒的生物学和治疗学进展

波及全球众多国家的严重急性呼吸道综合征(SARS)经初步鉴定是由新型冠状病毒引起的，了解冠状病毒的生物学和免疫学特点及其进化机制，有助于对SARS的预防和治疗提供有益启示。     

SARS冠状病毒PCR检测中的基因组比对研究

通过运用生物信息学的方法,对20株SARS冠状病毒基因组进行了多序列比对分析。所建立的20株SARS冠状病毒基因组之间的无根进化树,揭示了20株SARS冠状病毒基因组之间的同源性。在其多序列比对结果的基础上,对所设计的SARS冠状病毒PCR检测试剂盒的引物进行了分析,证明了该引物在全部20株SARS冠状病毒的PCR检测分析中的适用性。     

SARS疫苗动物试验

美国匹兹堡大学医学中心的研究人员研制出重组的严重急性呼吸道综合征(SARS)冠状病毒疫苗，并在动物模型中进行了试验。这一结果可能很快促成SARS疫苗的人体试验。     

SARS冠状病毒半胱氨酸蛋白酶3CLpro的克隆表达及分离纯化

SARS（严重急性呼吸综合征）是由一种新型的人类冠状病毒引起的。由于SARS冠状病毒3CL蛋白酶在病毒的复制翻译中起关键作用，所以成为抗SARS药物设计的关键靶标之一。该研究中，利用以pET28a为载体的高效原核表达系统，克隆表达出SARS冠状病毒3CL蛋白酶，然后由NTA-Ni^2＋亲和层析柱对表达的蛋白进行分离纯化。3CL蛋白酶在大肠杆菌表达系统中的成功表达为今后进一步筛选抗SARS病毒药物奠定基础。     

SARS病毒蛋白中caveolin推测的结合位点

目的：获得SARS冠状病毒蛋白与caveolin-1蛋白相互作用的信息,识别病毒蛋白中可能的caveolin-1结合位点,为SARS冠状病毒蛋白的功能研究以及设计抗SARS病毒的药物和疫苗提供线索．方法：基于3个caveolin结合基序,采用氨基酸基序搜索方法预测SARS冠状病毒蛋白中可能与caveolin-1相互作用的区域,并用分子模拟和分子对接的方法进一步证实它们之间的相互作用。结果：通过生物信息学分析,在SARS冠状病毒蛋白中发现了36个caveolin结合基序。经过分子模拟和分子对接,获得了SARS冠状病毒蛋白与caveolin-1相互作用的8个结合位点。这些caveolin-1结合位点分别位于replicase 1AB、S蛋白、ofr3蛋白和M蛋白．结论：caveolin-1可能是SARS冠状病毒蛋白结合的一个靶点,它们之间的相互作用可能与SARS冠状病毒的感染、复制、装配和释放有关。     

SARS病原初步查明

日前,科学家们已经完成导致严重急性呼吸综合征(SARS,即非典型肺炎)病毒的测序,并提议以确定SARS暴发流行和治疗越南首例SARS病人而染病身亡的Urbani医师命名该病毒——UrbaniSARS-相关冠状病毒(UrbaniSARS-     

SARS疫苗研究进展

严重急性呼吸综合征(severe acute respiratory syndrome,SARS)是由SARS相关冠状病毒(SARS-associated coronavirus,SARS-CoV)引起的一类严重的急性呼吸系统传染病.目前尚未研制出治疗SARS的有效药物,防范SARS-CoV感染最有效的方法是使用疫苗....     

SARS病原及其来源分析

自SARS爆发流行以来,我国大陆和香港、美国、加拿大等国家和地区均致力于其病原的研究,在分离到病毒的基础上对各分离株进行该病毒的全基因组序列分析,最终于4月16日由WHO正式宣布SARS的病原体为一种以前未知的新冠状病毒(Coronavirus),并命名为SARS冠状病毒(SARS-CoV)。     

Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro

The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the alpha-position were synthesized and tested as reversible inhibitiors against SARS 3CL(pro). Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC(50) values ranging from 0.60 to 70 microM.     

Sabadinine: a potential non-peptide anti-severe acute-respiratory-syndrome agent identified using structure-aided design

A novel human coronavirus has been reported to be the causative agent of severe acute respiratory syndrome (SARS). Since replication of HcoVs depends on extensive proteolytic processing, the main proteinase, 3CLpro, is an attractive drug target for anti-SARS agents. We have employed molecular docking of a chemical database into the active site of 3CLpro to search for non-peptidyl inhibitors. One compound was identified to be the natural product sabadinine, isolated from a historical herbal remedy.     

Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase

The SARS coronavirus 3C-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. In the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. The protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. Quantitative dissociation constants have been reported for the dimer by using analytic ultracentrifuge, gel filtration and enzyme assays. Though the enzyme is a cysteine protease with a chymotrypsin fold, SARS 3C-like proteinase follows the general base catalytic mechanism similar to chymotrypsin. As the enzyme can cut eleven different sites on the viral polyprotein, the substrate specificity has been studied by synthesized peptides corresponding or similar to the cleavage sites on the polyprotein. Predictive model was built for substrate structure and activity relationships and can be applied in inhibitor design. Due to the lack of potential drugs for the treatment of SARS, the discovery of inhibitors against SARS 3C-like proteinase, which can potentially be optimized as drugs appears to be highly desirable. Various groups have been working on inhibitor discovery by virtual screening, compound library screening, modification of existing compounds or natural products. High-throughput in vitro assays, auto-cleavage assays and viral replication assays have been developed for inhibition activity tests. Inhibitors with IC50 values as low as 60 nM have been reported.     

病毒3CL蛋白酶三维结构模型及其抑制剂的虚拟筛选(英文)

目的:构建SARS病毒类3C(3CL)蛋白酶的三维结构模型,根据这一模型设计3CL蛋白酶的抑制剂。方法:用生物信息学方法从GenBank和PDB库中搜寻出具有晶体结构并与SARS病毒3CL蛋白酶有较高同源型的蛋白质,以此为模板,用同源蛋白模建方法构建SARS病毒3CL蛋白酶的三维结构模型;针对模建的三维结构模型,进行高通量虚拟筛选,从现有小分子数据库中获得具有抑制SARS病毒3CL蛋白酶活性的化合物。结果:同源性分析表明SARS病毒3CL蛋白酶与遗传性肠胃炎主蛋白酶(TGEV M~(pro)),有较高的同源性,组成底物结合口袋残基的同源性更高。因此,可以根据TGEV M~(pro)的晶体结构为模板模建SARS病毒3CL蛋白酶的三维结构。 三维结构模型表明,ARS病毒3CL蛋白酶的结构与TGEV M~(pro)的结构非常相象,两个蛋白酶活性口袋的结构和形状儿乎一样。虚拟筛选测试研究表明,MRRD数据库中的73个蛋白酶抑制剂能与两个蛋白同时作用。结论:无论是SARS病毒3CL蛋白酶还是TGEV M~(pro)的晶体结构均可以作为设计抗SARS药物的结构模型。从现有的蛋白酶抑制剂中筛选抗SARS药物可能是一条好的途径。     

Recent patents on treatment of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is an epidemic that spread worldwide in early 2003. The aetiological agent was originally defined as a novel coronavirus and later designated as the SARS coronavirus (SARS-CoV), which appears similar to other coronaviruses in both virion structure and genome organization with a single-stranded, plus-sense RNA. However, the epidemiology and pathogenesis of SARS remain poorly understood and there is currently no effective treatment. To date, considerable research has been done on detection, prevention and treatment of SARS. In this review, we mainly focus on the recent patents and research work on detecting, preventing and treating SARS.     

Antiviral applications of RNAi for coronavirus

Until the appearance of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV) in early 2003, coronavirus infection was not considered to be serious enough to be controlled by either vaccination or specific antiviral therapy. It is now believed that the availability of antiviral drugs effective against SARS-CoV will be crucial for the control of future SARS outbreaks. Recently, RNA interference has been successfully used as a more specific and efficient method for gene silencing. RNA interference induced by small interfering RNA can inhibit the expression of viral antigens and so provides a new approach to the therapy of pathogenic viruses. This review provides an overview of current information on coronavirus and the application of small interfering RNA in viral therapeutics, with particular reference to SARS-CoV.     

Antiviral applications of RNAi for coronavirus

Until the appearance of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV) in early 2003, coronavirus infection was not considered to be serious enough to be controlled by either vaccination or specific antiviral therapy. It is now believed that the availability of antiviral drugs effective against SARS-CoV will be crucial for the control of future SARS outbreaks. Recently, RNA interference has been successfully used as a more specific and efficient method for gene silencing. RNA interference induced by small interfering RNA can inhibit the expression of viral antigens and so provides a new approach to the therapy of pathogenic viruses. This review provides an overview of current information on coronavirus and the application of small interfering RNA in viral therapeutics, with particular reference to SARS-CoV.     

Emerging viruses set to soar

The emergence rate of novel viruses, such as the coronavirus that sparked SARS, could well be on the rise.Researchers now think that the SARS virus split from group 2 coronaviruses, and that this happened relatively recently on the scale of coronavirus evolution.     

传染性非典型肺炎的临床诊断与治疗

目的 总结传染性非典型肺炎(SARS)的临床诊断与治疗经验。方法 对本院收治的2例SARS患，检测SARS病毒RNA，SARS病毒抗体，结合胸部X光片及病史、症状、体征进行综合诊断并给予无创呼吸机、抗生素、甲基强的松、胸腺肽、丙种球蛋白、白蛋白、速尿进行综合治疗。结果 2例SARS患，发病前均有流行病学接触史；发病期唾液、血液中SARS病毒RNA均为阳性；发病后12天，血液中出现SARS抗体IgM，16天出现SARS抗体IgG；SARS病毒可引起肺、心脏、肝脏、骨髓多脏器损伤；患T淋巴细胞CD3^ 、CD4^ 、CD8^ 明显减少；无创伤呼吸机的应用可明显改善患的血氧饱和度和血氧分压；经综合治疗，2例患均痊愈。结论 在对SARS进行诊断和鉴别诊断时，患的流行病学史及病原学检查至关重要；综合治疗是治愈SARS的有效治疗方法。