Single-molecule assays of the assembly/disassembly mechanisms of ssRNA viruses - Tools for screening novel anti-virals

ssRNA 病毒组装/分解机制的单分子分析 - 筛选新型抗病毒药物的工具

• 批准号: BB/J00667X/1
• 负责人: Peter Stockley
• 金额: $ 48.93万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ00667X%2F1
• 关键词: Single; molecule; assays; assembly; disassembly

Vaccination is one of the most successful medical interventions ever developed. However many viruses can not be controlled via this route for various technical reasons. Unlike bacterial infections that can be treated with antibiotics, there are currently very few drugs that can be used as anti-virals. We have recently discovered a promising novel route for the development of such anti-viral drugs and our proposal is to develop the tools needed for such a treatment strategy to become a reality. A critical part of any drug development porgramme is an assay to determine the effects of the drug, in this case the ability of our test virsues to assembly correctly. Standard experimental methods for this are expensive, time consuming and impractical. By using a technique called single-molecule fluoresence spectroscopy these problems can be avoided and we will be able to automate the assays allowing high-throughput screening for candidate drugs.

疫苗接种是有史以来最成功的医疗干预措施之一。然而，由于各种技术原因，许多病毒无法通过此途径进行控制。与可以用抗生素治疗的细菌感染不同，目前可以用作抗病毒药物的药物很少。我们最近发现了一种开发此类抗病毒药物的有前途的新途径，我们的建议是开发使这种治疗策略成为现实所需的工具。任何药物开发计划的一个关键部分是确定药物效果的测定，在本例中是我们的测试病毒正确组装的能力。标准实验方法昂贵、耗时且不切实际。通过使用单分子荧光光谱技术，这些问题可以避免，我们将能够实现检测自动化，从而对候选药物进行高通量筛选。

项目成果

Rewriting nature's assembly manual for a ssRNA virus.

• DOI: 10.1073/pnas.1706951114
• 发表时间: 2017-11-14
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Patel N;Wroblewski E;Leonov G;Phillips SEV;Tuma R;Twarock R;Stockley PG
• 通讯作者: Stockley PG

Direct Evidence for Packaging Signal-Mediated Assembly of Bacteriophage MS2.

• DOI: 10.1016/j.jmb.2015.11.014
• 发表时间: 2016-01-29
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Rolfsson Ó;Middleton S;Manfield IW;White SJ;Fan B;Vaughan R;Ranson NA;Dykeman E;Twarock R;Ford J;Kao CC;Stockley PG
• 通讯作者: Stockley PG

Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid.

• DOI: 10.1080/21597081.2016.1157666
• 发表时间: 2016-01
• 期刊: Bacteriophage
• 作者: Stockley PG;White SJ;Dykeman E;Manfield I;Rolfsson O;Patel N;Bingham R;Barker A;Wroblewski E;Chandler-Bostock R;Weiß EU;Ranson NA;Tuma R;Twarock R
• 通讯作者: Twarock R

The asymmetric structure of an icosahedral virus bound to its receptor suggests a mechanism for genome release.

• DOI: 10.1016/j.str.2013.05.012
• 发表时间: 2013-07-02
• 期刊: STRUCTURE
• 影响因子: 5.7
• 作者: Dent, Kyle C.;Thompson, Rebecca;Barker, Amy M.;Hiscox, Julian A.;Barr, John N.;Stockley, Peter G.;Ranson, Neil A.
• 通讯作者: Ranson, Neil A.

Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures.

• DOI: 10.1016/j.bpj.2016.10.014
• 发表时间: 2016-11-15
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Borodavka, Alexander;Singaram, Surendra W.;Stockley, Peter G.;Gelbart, William M.;Ben-Shaul, Avinoam;Tuma, Roman
• 通讯作者: Tuma, Roman