Faculty Sponsor(s)
John Frank
Subject Area
Biology
Description
SARS-CoV-2, the virus which caused the Covid-19 pandemic, likely jumped from bats into humans, canonically uses the protein ACE2 to infect cells. Recent studies found 22 possible human alternative receptors. However, it is unknown if these receptors are biologically significant to SARS-CoV-2 in vivo. Selective pressure between viruses and hosts often steer nucleotide changes in proteins, including viral receptors. Virus-driven natural selection is often evident in receptor evolution across related species. A signature of natural selection at virus-bound residues of an alternative receptor may indicate use by a virus. To determine if alternative SARS-CoV-2 receptors underwent natural selection in bats, established computational molecular evolution analysis tools were utilized in identifying sites of positive selection. 8 genes show signs of positive selection, with 2 having clustering in regions accessible by the virus. To test the functional relevance of the receptors to the virus, an experimental strategy was established. Human and bat alternative receptor sequences are cloned into expression plasmids and expressed in 293T cells, which are naturally resistant to SARS-CoV-2 infection. Then infected with SARS-CoV-2-spike pseudotyped VSV-luc reporter virus. These comprehensive studies will supply a deeper understanding of whether SARS-CoV-2 and related sarbecoviruses are likely to use alternative receptors in bats.
Recommended Citation
Harris, Kayden; Price, Aemelia; and Bentz, Ruby, "Using Molecular Evolution to Explore Alternative Receptors for SARS-CoV-2" (2026). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 10.
https://digitalcommons.linfield.edu/symposium/2026/all/10
Using Molecular Evolution to Explore Alternative Receptors for SARS-CoV-2
SARS-CoV-2, the virus which caused the Covid-19 pandemic, likely jumped from bats into humans, canonically uses the protein ACE2 to infect cells. Recent studies found 22 possible human alternative receptors. However, it is unknown if these receptors are biologically significant to SARS-CoV-2 in vivo. Selective pressure between viruses and hosts often steer nucleotide changes in proteins, including viral receptors. Virus-driven natural selection is often evident in receptor evolution across related species. A signature of natural selection at virus-bound residues of an alternative receptor may indicate use by a virus. To determine if alternative SARS-CoV-2 receptors underwent natural selection in bats, established computational molecular evolution analysis tools were utilized in identifying sites of positive selection. 8 genes show signs of positive selection, with 2 having clustering in regions accessible by the virus. To test the functional relevance of the receptors to the virus, an experimental strategy was established. Human and bat alternative receptor sequences are cloned into expression plasmids and expressed in 293T cells, which are naturally resistant to SARS-CoV-2 infection. Then infected with SARS-CoV-2-spike pseudotyped VSV-luc reporter virus. These comprehensive studies will supply a deeper understanding of whether SARS-CoV-2 and related sarbecoviruses are likely to use alternative receptors in bats.