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）已在人类中引起两次严重流行病（MERS-CoV和SARS-CoV）和当前的COVID-19大流行病（SARS-CoV 2）。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对当前大流行性冠状病毒（SARS-CoV 2）易感的动物种群，并可能作为病毒储存库并引发新的疾病爆发。确定动物受体，使SARS-CoV 2细胞进入将有利于人类和动物的健康，指导未来的研究冠状病毒嗜性。这些知识还将把监测工作的重点放在最有可能参与SARS-CoV 2和其他CoV的人畜共患病和逆转人畜共患病传播的物种上。这项建议将在拟议的项目期间培训本科研究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，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实验室研究来识别赋予SARS-CoV 2易感性的动物血管紧张素转换酶2（ACE 2）细胞受体。研究人员将测试动物ACE 2中的某些氨基酸残基对于冠状病毒（CoV）刺突蛋白相互作用和细胞进入至关重要的假设。将开发一个计算管道，以模拟SARS-CoV 2受体结合域与数百种不同动物物种的ACE 2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来经验性地测试SARS-CoV 2刺突蛋白利用ACE 2的能力。这项研究有可能识别出对SARS-CoV 2易感的广泛动物物种。这将有助于理解ACE 2基因型和SARS-CoV 2细胞进入之间的关系，并允许预测ACE 2残基，这对确定CoV易感性至关重要。 这个快速奖是由共生，防御和自我识别计划在生物综合有机系统部，并由既定计划，以刺激竞争力的研究（EPSCoR），使用资金从冠状病毒援助，救济，经济安全（CARES）该奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的支持影响审查标准。

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.