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.

现在，我们生活在新型冠状病毒（SARS-COV-2）菌株中，全世界有大量确认病例。正在进行几项努力，以产生新药物抑制剂，重新利用现有药物并设计联合治疗。同时，疫苗发育既靶向针对病毒的包膜蛋白的中和抗体，又是基于T细胞淋巴细胞的长期细胞介导的免疫。 T细胞反应对于打击病毒感染尤其重要，因为它们可以找到并消除受感染的细胞。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），这些蛋白可以用作基于广谱肽的广谱疫苗的靶标，这些疫苗可以提供针对几种SARS-COV-2菌株的保护性免疫，并具有其他SARS-COV-2和其他潜在的类似SARS类冠状病毒。该工作流程将由广泛的病毒学研究界共享，任何已鉴定的肽都将直接与SARS-COV变体和其他病原体研究直接相关，该研究将缩短疫苗和药物发育周期，对于任何可能的新冠状病毒。通过研究生和DOC研究指导，专业发展和职业指导来教育和培训未来的研究人员。 该项目将开发一条计算管道，以实现在不同SARS-COV菌株中保守的肽的鉴定，并有可能用于诱导针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方法的联合使用，以及与与不同人类白细胞抗原（HLA）受体结合的肽结构建模和分析的新尖端方法。 HLA负责向T细胞淋巴细胞显示肽，并且所提出的管道将使能够鉴定能够针对多个SARS-COV变体触发T细胞响应的保守热点。在该项目的背景下，研究将靶向SARS-COV-2的核素蛋白（N）蛋白质的保守肽。如果需要，将针对不同流行的HLA等位基因进行预测的肽。拟议的计算管道将使用一般软件工程原理构建，也适用于研究SARS-COV变体甚至其他病原体的不同蛋白质。可以在http://www.kavrakilab.org/nsf-rapid-sarscov2.html中找到此快速奖励，这一快速奖励是由生物研究基础设施创新（IIBR Informatics）计划在生物基础设施中使用Coronavirus AID，RELSIER，RELLIEF，RELLIEF，RELLIEF，RELLIEF，RELLIECT（RELLIEC）的资金（法定任务，并被认为是值得通过基金会的智力优点和更广泛影响的审查标准来评估的值得支持的。