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

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.