Novel organic-ion-based technology for long-term virus preservation at ambient temperature

基于有机离子的新型技术，可在环境温度下长期保存病毒

基本信息

批准号：
10369847
负责人：
Scott F Michael
金额：
$ 2.73万
依托单位：
FLORIDA GULF COAST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369847
关键词：
Accounting Acids Affect Ammonium Anions Bacteriophages Base Pairing Benign Binding Biological Assay Buffers COVID-19 COVID-19 vaccine Capsid Proteins Carbon Cations Characteristics Circular Dichroism Spectroscopy Cold Chains Cryopreservation DNA Dengue Virus Developing Countries Development Differential Scanning Calorimetry Effectiveness Electrostatics Enzymes Exhibits Family Fluorides Formulation Freezing Future Goals Hydration status Hydrogen Bonding Hydrolysis Ions Knowledge Libraries Life Lipid Bilayers Lipids Liquid substance Logistics Lytic Maintenance Medicine Messenger RNA Methods Mind Modeling Molecular Monitor Morphology Names Nature Nucleic Acid Vaccines Nucleic Acids Outcome Polymerase Chain Reaction Procedures Process Production Property Proteins Protocols documentation Quantitative Structure-Activity Relationship Recombinant Proteins Recovery Resource-limited setting Resources Reverse Transcription Roentgen Rays Salts Sampling Savings Scanning Scientist Solvents Structure Structure-Activity Relationship Techniques Technology Temperature Time Toxicology Transmission Electron Microscopy Transportation Vaccination Vaccines Variant Viral Viral Genome Viral Proteins Virus Virus-like particle Water aqueous base biobank biomaterial compatibility cost cost effective cytotoxicity design fighting flu functional group global health improved light scattering liquid formulation neglect novel novel vaccines nucleic acid stability pandemic disease particle preservation prevent programs rational design simulation solute stressor technology development thermostability vaccination outcome vaccine access vaccine distribution water diffusion

项目摘要

PROJECT SUMMERY Most currently available vaccines, especially live and mRNA-based COVID-19 vaccines, are temperature sensi- tive and require stringent cold-chain maintenance, entailing their storage and distribution at recommended tem- peratures from production to administration. This necessity imposes the most prohibitive barrier to global im- munization programs, particularly in developing countries, accounting for up to 80% of the cost delivery. Thus, there is a critical need for a technology to provide cost-effective and long-term ambient temperature storage for viral samples without requiring cold chain or complicated sample recovery protocols. This proposal aims to develop an organic-ion platform for long-term storage of viruses at ambient tem- perature to potentially reduce costs in the face of growing needs for new vaccines and avoid labor-intensive maintenance associated with current biobanking technology. Ionic liquids (ILs)  organic salts comprised entirely of ions  offer a well-suited platform on which the properties can be altered by the selection of ions, enabling the tunable design of solvents/media for virus stabilization. We hypothesize that the solutions of proposed ILs with ca. 20 wt% water may prevent hydrolytic and enzymatic degradation of viral genomes and protein capsids, providing a reliable approach to preserve viruses. We will use a bacteriophage from the myovirus family as an example of a naked protein particle and dengue virus as an example of a lipid-enveloped particle. First, we will develop a thoughtfully conceived library of novel ILs through systematic variations of heterocyclic cations and kosmotropic anions, and judicious incorporation of two functionalities (NH3+ and SO2F) into the IL structures. Structural variability will be achieved by pairing new genre of biocompatible cations and anions. Second, we will examine their effectiveness for stabilizing viruses by evaluating their structural integrity, thermostability, and shelf-life from six months and four year. We will monitor changes in viral secondary structure, thermal denatur- ation, and particle morphology. Last, we will study their empirical structure-activity relationships to gain compre- hensive understanding of binding characteristics and molecular mechanisms of interactions between the viral particles and the targeted aqueous ionic solvents via simulation, crystallographic, and spectroscopic methods. This project will provide a viable solution for ambient temperature preservation of viruses for extended periods (potentially for decades) by developing the virusILwater matrices that are stable towards hydrolytic and enzymatic degradation. Another important feature of the proposed approach is that these nucleic acid-ILs solutions can be directly amplified by PCR without being subjected to prior extraction, purification or quantifica- tion. This approach has the merit of simplicity, which makes the process of ambient temperature storage and distribution profoundly efficient, increases the stability of biosamples for prolonged time, reduces operational costs and carbon footprint, and improves logistics for viruses and virus-based technologies. Summery

夏季项目当前大多数可用的疫苗，尤其是实时和基于mRNA的COVID-19疫苗，是温度敏感的需要严格的冷链维护，需要以推荐的温度进行存储和分配从生产到管理的耕种。这种必要的不可能是全球影响最多的障碍推出计划，特别是在发展中国家，最多占成本交付的80％。那，技术需要一项技术来提供具有成本效益和长期环境温度存储病毒样品无需冷链或复杂的样品恢复方案。该建议旨在开发一个有机离子平台，用于在环境温度上长期存储病毒面对新疫苗的需求不断增长并避免实验室密集型，可以潜在地降低成本维护与当前的生物库技术相关。离子液体（ILS）有机盐完全完成离子的OF IONT提供了一个合理的平台，可以通过选择离子来改变该属性用于病毒稳定的解决方案/培养基的可调设计。我们假设提议的IL的解决方案与大约20 wt％的水可以防止病毒基因组和蛋白质衣壳的水解和酶促降解，提供一种可靠的方法来保存病毒。我们将使用Myovirus家族的细菌作为一个裸蛋白颗粒和登革热病毒的例子，作为脂质发育颗粒的一个例子。首先，我们会的通过杂环阳离子的系统变化和 Kosmotropic阴离子和两个功能（NH3+和SO2F）的合理结合结合到IL结构中。结构可变性将通过配对新型的生物相容性阳离子和阴离子。第二，我们会的通过评估其结构完整性，热稳定性和六个月零四年的保质期。我们将监视病毒二级结构的变化，热变性 - ation和粒子形态。最后，我们将研究他们的经验结构活动关系，以获得综合对病毒之间相互作用的结合特征和分子机制的Hansive理解通过模拟，晶体学和光谱方法，颗粒和靶向水溶液溶液。该项目将为环境温度保存病毒的延长提供可行的解决方案通过开发对水解稳定的病毒矩阵（可能数十年）（可能数十年）和酶促降解。提出方法的另一个重要特征是这些核酸-IL 可以通过PCR直接扩增溶液，而不会受到事先提取，纯化或定量 tion。这种方法具有简单性的优点，这使环境温度存储和分布非常高效，增加了长时间生物样本的稳定性，减少了运营成本和碳足迹，改善了病毒和基于病毒的技术的物流。夏天