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适体BC 007——新冠病毒关键传播蛋白的高效结合剂。

Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins.

作者信息

Weisshoff Hardy, Krylova Oxana, Nikolenko Heike, Düngen Hans-Dirk, Dallmann Andre, Becker Susanne, Göttel Peter, Müller Johannes, Haberland Annekathrin

机构信息

Department of Chemistry, NMR Facility, Humboldt University of Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany.

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany.

出版信息

Heliyon. 2020 Nov;6(11):e05421. doi: 10.1016/j.heliyon.2020.e05421. Epub 2020 Nov 2.

Abstract

Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses a serious global public health emergency. To date 32,174,627 cases, of which 962,613 (2.99%) have died, have been reported (https://www.who.int/westernpacific/health-topics/coronavirus, accessed 23 Sep 2020). The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. There are still not many SARS-CoV-2-specific and effective treatments or vaccines available. A second round of infection is obviously unavoidable. Aptamers had already been at the centre of interest in the fight against viruses before now. The selection and development of a new aptamer is, however, a time-consuming process. We therefore checked whether a clinically developed aptamer, BC 007, which is currently in phase 2 of clinical testing for a different indication, would also be able to efficiently bind DNA-susceptible peptide structures from SARS-CoV-2-spreading crucial proteins, such as the receptor binding domain (RBD) of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2 (re-purposing). Indeed, several such sequence-sections have been identified. In particular for two of these sequences, BC 007 showed specific binding in a therapy-relevant concentration range, as shown in Nuclear magnetic resonance (NMR)- and Circular dicroism (CD)-spectroscopy and isothermal titration calorimetry (ITC). The excellent clinical toxicity and tolerability profile of this substance opens up an opportunity for rapid clinical testing of its COVID-19 effectiveness.

摘要

2019年冠状病毒病(COVID-19)是一种由新型冠状病毒(SARS-CoV-2)引起的呼吸道疾病,可导致严重的发病和死亡。这种新型高致病性SARS-CoV-2的出现及其在国际上的迅速传播构成了严重的全球公共卫生紧急事件。截至目前,已报告32174627例病例,其中962613例(2.99%)死亡(https://www.who.int/westernpacific/health-topics/coronavirus,访问时间:2020年9月23日)。2020年1月30日,该疫情被宣布为国际关注的突发公共卫生事件。目前仍没有许多针对SARS-CoV-2的特异性有效治疗方法或疫苗。第二轮感染显然不可避免。在此之前,适配体就已成为抗击病毒的关注焦点。然而,新适配体的筛选和开发是一个耗时的过程。因此,我们检查了一种临床开发的适配体BC 007,它目前正处于针对不同适应症的临床试验第二阶段,是否也能够有效结合来自SARS-CoV-2传播关键蛋白(如刺突蛋白的受体结合域(RBD)和SARS-CoV-2的RNA依赖性RNA聚合酶)的易受DNA影响的肽结构(重新利用)。事实上,已经鉴定出了几个这样的序列片段。特别是对于其中两个序列,BC 007在与治疗相关的浓度范围内表现出特异性结合,如在核磁共振(NMR)、圆二色性(CD)光谱和等温滴定量热法(ITC)中所示。该物质出色的临床毒性和耐受性概况为快速进行其COVID-19有效性的临床试验提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b94/7648198/31bd16aa162c/gr1.jpg

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