RAPID: Comparative genomics of SARS-CoV-2 susceptibility and immune defense in mammals

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The goal of this project is to compare genomes of hundreds of mammal species, finding differences in DNA that distinguish species resistant to SARS-CoV-2 from those that are very susceptible. This information is needed to understand how the current SARS-CoV-2 virus spread to humans and to identify potential host animals (e.g., pet, livestock, and pest species) that may be susceptible to SARS-CoV-2 in the USA. SARS-CoV-2, the cause of the COVID-19 pandemic, can infect diverse species of animals. There is a variation in susceptibility to and severity of disease between species. This variation suggests that some species have genetic differences that dictate susceptibility to COVID-19. This work will identify how coronaviruses adapt to new host species, information that will help predict and control future coronavirus outbreaks. Funding will support training a graduate student in research, thereby training the next generation of the bioeconomy workforce. This project will investigate how the host genome shapes host-pathogen interactions, and how coronaviruses like SARS-CoV-2 evolve to exploit new hosts. The researchers will compare existing genomic data for hundreds of mammals using three complementary approaches: (1) Measure structural and sequence homology in two host proteins, ACE2 and TMPRSS2, necessary for infection in humans; (2) Analyze existing RNA-seq datasets to (a) identify species with co-expression of ACE2 and TMPRSS2, and potentially other proteases implicated in infection, in the same tissue, and (b) search for incidental coronaviral sequence data from diverse mammalian species; (3) Test for variants in evolutionarily conserved elements that are correlated with species susceptibility, using forward genomics. With these analyses, the researchers will identify species with potential as reservoirs for SARS-CoV-2 viral spillback into humans, and those that are promising systems for investigating SARS-CoV-2 evolution, host defenses, and host-pathogen interactions. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, 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.