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EAGER: Rapid and Sensitive Drug Testing for COVID-19

EAGER：快速、灵敏的 COVID-19 药物检测

基本信息

批准号：
2030750
负责人：
John Yin
金额：
$ 20万
依托单位：
University of Wisconsin-Madison
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：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2030750&HistoricalAwards=false
关键词：
EAGER Rapid Sensitive Drug Testing

项目摘要

With vaccines against the COVID-19 pandemic still months-to-years away, current treatments for infected patients focus on anti-viral drugs. However, like many viruses that cause serious morbidity and mortality, coronaviruses can mutate and develop drug resistance. Effective treatment may require the availability of multiple effective drugs. Thousands of drug candidates are available, but a current bottleneck is drug testing, which entails virus growth in cell cultures, a labor intensive, low sensitivity, and time-consuming process that can take up to a week to perform. ThIs EAGER project exploits microscopic fluid flows in cell and virus cultures to enhance sensitivity and speed, potentially reducing test times to one day. The project aims to identify best conditions for testing of drugs against the COVID-19 virus, which will expand opportunities to effectively treat infected patients.The gold standard for testing anti-viral drugs is the plaque assay, which gives direct measures of drug effect on the production and spread of infectious virus particles in the cell culture. However, the plaque assay is labor-intensive, limited in sensitivity for drug testing, and it can take a week to perform. As an alternative, a team with expertise in virology and fluid dynamics will advance a faster, more sensitive assay. The approach exploits flow-enhanced infection spread and automated quantitative imaging, which they will optimize for coronavirus drug testing. The technology exploits microscale flows that sweep across infected cells, enhancing the spread of infection; in cell-culture wells, radial flows spontaneously arise from enhanced evaporative cooling at the fluid surface near the center of the each well, driving natural convection. The project may enable a 10-to100-fold higher sensitivity in one-tenth the time for testing drug candidates against COVID-19. Such accelerated testing could help efficiently identify drugs that significantly reduce morbidity and mortality from the ongoing pandemic and its possible re-emergence.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.

由于针对COVID-19大流行的疫苗仍需数月至数年时间，目前对感染患者的治疗主要集中在抗病毒药物上。然而，像许多导致严重发病率和死亡率的病毒一样，冠状病毒可以发生突变并产生耐药性。有效的治疗可能需要多种有效药物的可用性。成千上万的候选药物是可用的，但目前的瓶颈是药物测试，这需要细胞培养中的病毒生长，这是一个劳动密集型，低灵敏度和耗时的过程，可能需要长达一周的时间来执行。这个EAGER项目利用细胞和病毒培养物中的微观流体流动来提高灵敏度和速度，可能将测试时间缩短到一天。该项目旨在确定测试抗COVID-19病毒药物的最佳条件，这将扩大有效治疗感染患者的机会。测试抗病毒药物的金标准是空斑试验，它可以直接测量药物对细胞培养物中传染性病毒颗粒的产生和传播的影响。然而，空斑检测是劳动密集型的，对药物检测的灵敏度有限，并且可能需要一周的时间才能完成。作为替代方案，一个具有病毒学和流体动力学专业知识的团队将推进更快、更灵敏的检测。该方法利用了流动增强的感染传播和自动定量成像，他们将优化冠状病毒药物测试。该技术利用微尺度流动扫过受感染的细胞，增强感染的传播;在细胞培养威尔斯孔中，径向流动自发地产生于每个孔中心附近的流体表面处的增强的蒸发冷却，从而驱动自然对流。该项目可能在十分之一的时间内实现10至100倍的灵敏度，用于测试针对COVID-19的候选药物。这种加速测试可以帮助有效地识别可显着降低持续大流行及其可能再次出现的发病率和死亡率的药物。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的知识进行评估而被认为值得支持影响审查标准。