IIBR:Informatics:RAPID: Structure-based identification of SARS-derived peptides with potential to induce broad protective immunity

IIBR：信息学：RAPID：基于结构的 SARS 衍生肽的鉴定，具有诱导广泛保护性免疫的潜力

• 批准号: 2033262
• 负责人: Lydia Kavraki
• 金额: $ 11.97万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2033262&HistoricalAwards=false
• 关键词: IIBR; Informatics; RAPID; Structure; based

We are now living through a pandemic age caused by a novel strain of coronavirus (SARS-CoV-2) with a fast-growing number of confirmed cases all over the world. Several efforts are underway to produce new drug inhibitors, repurpose existing drugs and devise combination treatments. At the same time, vaccine development is targeting both neutralizing antibodies against envelope proteins of the virus, and long-term cell-mediated immunity based on T cell lymphocytes. T cell responses are particularly important for fighting viral infections, because they can find and eliminate infected cells. This project will use advanced methods of computational structural analysis to identify conserved small fragments (peptides) of SARS-CoV-2 viral proteins that can be used as targets for a broad-spectrum peptide-based vaccine, which could provide protective immunity against several strains of SARS-CoV-2 and potentially other SARS-like coronaviruses. The workflow will be shared by broad virology research community and any identified peptides will be directly related to SARS-CoV variants and other pathogen study, which will shorten vaccine and drug development cycle for any possible future new coronaviruses. Educating and training future researchers are planned through graduate and post-doc research mentoring, professional development, and career guidance. This project will develop a computational pipeline to enable the identification of peptides that are conserved across different SARS-CoV strains, and that can potentially be used to induce broad protective cellular immunity against these viruses. The approach is based on the combined use of gold-standard sequence-based methods, and new cutting-edge methods for the structural modeling and analysis of peptides bound to different Human Leukocyte Antigen (HLA) receptors. HLAs are responsible for displaying the peptides to T-cell lymphocytes, and the proposed pipeline will enable the identification of conserved hot-spots capable of triggering T-cell responses against multiple SARS-CoV variants. In the context of this project, research will target conserved peptides from the Nucleocapsid (N) protein of SARS-CoV-2. If needed, optimization of predicted peptides will be conducted for different prevalent HLA alleles. The proposed computational pipeline will be built using general software-engineering principles, making it also applicable to study different proteins from SARS-CoV variants, and even other pathogens. The work done on this project can be found in http://www.kavrakilab.org/nsf-rapid-sarscov2.html This RAPID award is made by the Infrastructure Innovation for Biological Research (IIBR Informatics) Program in the Division of Biological Infrastructure, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

我们现在生活在由一种新的冠状病毒株(SARS-CoV-2)引起的大流行时代，世界各地的确诊病例数量迅速增加。目前正在进行几项努力，以生产新的药物抑制剂，重新调整现有药物的用途，并设计出联合治疗方法。与此同时，疫苗的开发既针对针对病毒包膜蛋白的中和抗体，也针对基于T细胞淋巴细胞的长期细胞介导免疫。T细胞反应对于对抗病毒感染特别重要，因为它们可以发现并清除受感染的细胞。该项目将使用先进的计算结构分析方法来识别SARS-CoV-2病毒蛋白的保守小片段(肽)，这些片段(肽)可以用作广谱多肽疫苗的靶标，这种疫苗可以对几种SARS-CoV-2毒株和可能的其他类似SARS冠状病毒提供保护性免疫。这一工作流程将由广泛的病毒学研究团体共享，任何已发现的多肽都将直接与SARS-CoV变种和其他病原体研究有关，这将缩短未来任何可能出现的新冠状病毒的疫苗和药物开发周期。通过研究生和博士后研究指导、专业发展和职业指导来计划教育和培训未来的研究人员。该项目将开发一种计算管道，以能够识别在不同SARS-CoV毒株之间保守的多肽，并有可能用于诱导对这些病毒的广泛保护性细胞免疫。该方法基于基于金标准序列的方法和新的尖端方法的组合使用，用于与不同的人类白细胞抗原(人类白细胞抗原)受体结合的多肽的结构建模和分析。HLA负责将多肽展示给T细胞淋巴细胞，拟议的管道将能够识别能够触发T细胞对多种SARS-CoV变种的反应的保守热点。在这个项目的背景下，研究将以SARS-CoV-2核衣壳(N)蛋白中的保守肽为目标。如果需要，将针对不同流行的HLA等位基因进行预测多肽的优化。拟议的计算管道将使用通用的软件工程原理建立，使其也适用于研究SARS-CoV变种的不同蛋白质，甚至其他病原体。在这个项目上所做的工作可以在http://www.kavrakilab.org/nsf-rapid-sarscov2.html上找到。这个快速奖是由生物基础设施部的生物研究基础设施创新(IIBR信息学)计划做出的，使用冠状病毒援助、救济和经济安全(CARE)法案的资金。这个奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。