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SARS-CoV-2 的理化性质及其在药物靶向、病毒失活与减毒、疫苗配方和质量控制方面的应用。

Physicochemical properties of SARS-CoV-2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control.

机构信息

Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Braunschweig, Germany.

出版信息

Electrophoresis. 2020 Jul;41(13-14):1137-1151. doi: 10.1002/elps.202000121. Epub 2020 Jun 8.

Abstract

The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its proteins are discussed. We review the viral structure, size, rigidity, lipophilicity, isoelectric point, buoyant density and centrifugation conditions, stability against pH, temperature, UV light, gamma radiation, and susceptibility to various chemical agents including solvents and detergents. Possible inactivation, downstream, and formulation conditions are given including suitable buffers and some first ideas for quality-control methods. This information supports vaccine development and discussion with competent authorities during vaccine approval and is certainly related to drug-targeting strategies and hygienics. Several instructive tables are given, including the pI and grand average of hydropathicity (GRAVY) of SARS-CoV-1 and -2 proteins in comparison. SARS-CoV-1 and SARS-CoV-2 are similar in many regards, so information can often be derived. Both are unusually stable, but sensitive at their lipophilic membranes. However, since seemingly small differences can have strong effects, for example, on immunologically relevant epitope settings, unevaluated knowledge transfer from SARS-CoV-1 to SARS-CoV-2 cannot be advised. Published knowledge regarding downstream processes, formulations and quality assuring methods is, as yet, limited. However, standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.

摘要

讨论了严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)及其蛋白的物质特性。我们回顾了病毒的结构、大小、刚性、亲脂性、等电点、浮力密度和离心条件,以及对 pH 值、温度、紫外线、γ 辐射的稳定性,以及对各种化学制剂的敏感性,包括溶剂和去污剂。给出了可能的失活、下游和制剂条件,包括合适的缓冲液和一些质量控制方法的初步想法。这些信息支持疫苗的开发,并在疫苗批准过程中与主管部门进行讨论,与药物靶向策略和卫生学密切相关。文中还给出了几个有启发性的表格,包括 SARS-CoV-1 和 -2 蛋白的等电点和平均亲水性(GRAVY)的比较。SARS-CoV-1 和 SARS-CoV-2 在许多方面都相似,因此通常可以从 SARS-CoV-1 中获得信息。两者都非常稳定,但对亲脂性膜敏感。然而,由于即使是微小的差异也可能产生强烈的影响,例如对免疫相关表位的影响,因此不能建议未经评估的知识从 SARS-CoV-1 向 SARS-CoV-2 的转移。关于下游工艺、制剂和质量保证方法的已发表知识目前还很有限。然而,似乎对于其他病毒和疫苗采用的标准方法是可行的,包括病毒失活、离心条件以及佐剂的使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d116/7283733/d54c78dc57c5/ELPS-41-1137-g001.jpg

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