RAPID: The potential of SARS-CoV2 to utilize the ACE2 receptor of domesticated and wild animals for cell entry.

人畜共患冠状病毒（cov）已经在人类中引起了两次严重的流行病（MERS-CoV和SARS-CoV）和当前的COVID-19大流行（SARS-CoV2）。有证据表明，尽管这些冠状病毒起源于蝙蝠，但其他哺乳动物可能是将病毒传播给人类的中间宿主。该奖项支持的研究将有助于确定可能易受当前大流行冠状病毒（SARS-CoV2）影响的动物种群，这些种群可能充当病毒宿主并引发新的疾病暴发。确定能够使SARS-CoV2细胞进入的动物受体将通过指导未来的冠状病毒趋向性研究而有益于人类和动物健康。这方面的知识还将把监测工作重点放在最有可能参与SARS-CoV2和其他冠状病毒人畜共患传播和反向人畜共患传播的物种上。该提案将在提议的项目中训练本科生的计算和实验室技能。这些研究的结果将发表在同行评议的期刊上，在科学会议上发表，发布到共享数据库中，并通过社交媒体分享。该奖项支持的研究将采用计算建模和经验实验室研究，以确定赋予SARS-CoV2易感性的动物血管紧张素转换酶2 （ACE2）细胞受体。研究人员将验证一种假设，即动物ACE2中的某些氨基酸残基对冠状病毒（CoV）刺突蛋白相互作用和细胞进入至关重要。将开发一个计算管道来模拟和模拟来自数百种不同动物物种的SARS-CoV2受体结合域与ACE2细胞受体的对接。我们还将通过异源表达系统和体外细胞培养研究，实证检验SARS-CoV2刺突蛋白利用ACE2的能力。这项研究有可能确定对SARS-CoV2易感的广泛动物物种。这将有助于理解ACE2基因型与SARS-CoV2细胞进入之间的关系，并允许预测ACE2残基，这对确定冠状病毒易感性至关重要。该RAPID奖由综合有机体系统生物部门的共生、防御和自我识别计划以及刺激竞争研究的既定计划（EPSCoR）颁发，使用冠状病毒援助、救济和经济安全（CARES）法案的资金。该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知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Zoonotic coronaviruses (CoVs) have caused two serious epidemics in humans (MERS-CoV and SARS-CoV) and the current COVID-19 pandemic (SARS-CoV2). There is evidence suggesting that although these CoVs originated from bats, other mammals could have been intermediate hosts that transmitted the virus to humans. Research supported by this award will help to identify animal populations that are likely susceptible to the current pandemic CoV (SARS-CoV2) and could potentially act as viral reservoirs and initiate new disease outbreaks. Determining the animal receptors that enable SARS-CoV2 cell entry will benefit both human and animal health by directing future studies of CoV tropism. This knowledge will also focus surveillance efforts to species most likely involved in zoonotic and reverse zoonotic transmission of SARS-CoV2 and other CoVs. This proposal will train undergraduate research students in computational and laboratory skills during the proposed project. Results from these studies will be published in peer-reviewed journals, presented at scientific meetings, posted to shared data repositories, and also shared through social media.Research supported by this award will employ computational modeling and empirical laboratory research to identify animal angiotensin converting-enzyme 2 (ACE2) cell receptors that confer susceptibility to SARS-CoV2. Researchers will test the hypothesis that certain amino acid residues in animal ACE2 are essential for coronavirus (CoV) spike protein interaction and cell entry. A computational pipeline will be developed to model and simulate the docking of the SARS-CoV2 receptor binding domain to the ACE2 cell receptor from hundreds of divergent animal species. We will also empirically test the capacity of SARS-CoV2 spike protein to utilize ACE2 through heterologous expressions systems and in vitro cell culture studies. The research has the potential to identify a wide spectrum of animal species that are susceptible to SARS-CoV2. This will aid in the understanding of the relationship between ACE2 genotype and SARS-CoV2 cell entry and allow the prediction of ACE2 residues that are critical for determining CoV susceptibility. This RAPID award is made by the Symbiosis, Defense, and Self-recognition Program in the BIO Division of Integrative Organismal Systems, and by the Established Program to Stimulate Competitive Research (EPSCoR), 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.