严重急性呼吸综合征（SARS-CoV）诊断与治疗的分子靶点
Molecular targets for diagnostics and therapeutics of severe acute respiratory syndrome (SARS-CoV).
作者信息
Suresh Mavanur R, Bhatnagar Pravin K, Das Dipankar
机构信息
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
出版信息
J Pharm Pharm Sci. 2008 Apr 19;11(2):1s-13s. doi: 10.18433/j3j019.
PURPOSE
The large number of deaths in a short period of time due to the spread of severe acute respiratory syndrome (SARS) infection led to the unparalleled collaborative efforts world wide to determine and characterize the new coronavirus (SARS-CoV). The full genome sequence was determined within weeks of the first outbreak by the Canadian group with international collaboration. As per the World Health Organization (WHO), the continual lack of a rapid laboratory test to aid the early diagnosis of suspected cases of SARS makes this area a priority for future research. To prevent deaths in the future, early diagnosis and therapy of this infectious disease is of paramount importance.
METHODS
This review describes the specific molecular targets for diagnostics and therapeutics of viral infection.
RESULTS
The three major diagnostic methods available for SARS includes viral RNA detection by reverse transcription polymerase chain reaction (RT-PCR), virus induced antibodies by immunofluorescence assay (IFA) or by enzyme linked immunosorbant assay (ELISA) of nucleocapsid protein (NP). The spike glycoprotein of SARS-CoV is the major inducer of neutralizing antibodies. The receptor binding domain (RBD) in the S1 region of the spike glycoprotein contains multiple conformational epitopes that induces highly potent neutralizing antibodies. The genetically engineered attenuated form of the virus or viral vector vaccine encoding for the SARS-CoV spike glycoprotein has been shown to elicit protective immunity in vaccinated animals.
CONCLUSION
NP is the preferred target for routine detection of SARS-CoV infection by ELISA which is an economical method compared to other methods. The RBD of the spike glycoprotein is both a functional domain for cell receptor binding and also a major neutralizing determinant of SARS-CoV. The progress in evaluating a therapeutic or vaccine would depend on the avail ability of clinically relevant animal model.
目的
严重急性呼吸综合征（SARS）感染的传播导致在短时间内出现大量死亡病例，这促使全球展开了前所未有的合作，以确定新型冠状病毒（SARS-CoV）并对其进行特征描述。在首次疫情爆发后的数周内，加拿大团队通过国际合作确定了其全基因组序列。根据世界卫生组织（WHO）的说法，持续缺乏快速实验室检测手段来辅助SARS疑似病例的早期诊断，使得该领域成为未来研究的重点。为预防未来出现死亡病例，对这种传染病进行早期诊断和治疗至关重要。
方法
本综述描述了病毒感染诊断和治疗的特定分子靶点。
结果
可用于SARS的三种主要诊断方法包括通过逆转录聚合酶链反应（RT-PCR）检测病毒RNA、通过免疫荧光测定（IFA）或核衣壳蛋白（NP）的酶联免疫吸附测定（ELISA）检测病毒诱导的抗体。SARS-CoV的刺突糖蛋白是中和抗体的主要诱导物。刺突糖蛋白S1区域的受体结合域（RBD）包含多个构象表位，可诱导高效中和抗体。已证明，经基因工程减毒的病毒形式或编码SARS-CoV刺突糖蛋白的病毒载体疫苗可在接种动物中引发保护性免疫。
结论
NP是通过ELISA常规检测SARS-CoV感染的首选靶点，与其他方法相比，这是一种经济的方法。刺突糖蛋白的RBD既是细胞受体结合的功能域，也是SARS-CoV的主要中和决定因素。评估治疗方法或疫苗的进展将取决于临床相关动物模型模型的可用性。
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