New “ViraMap” Technology Has Potential to Identify Entry Mechanisms of Viruses Affecting Humans

Recent research out of Boston University highlights host targets that participate in SARS-CoV-2 infection and showcases ViraMap as a powerful platform for studying viral interactions on the surface of cells.

By Mohsan Saeed, Assistant Professor, Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine

Mohsan Saeed at computerA precise mapping of interactions between proteins on the surface of a cell can offer important insights into cell biology, as well as into communications and interactions between cells and pathogens. A recently introduced approach, which relies on photo-proximity labeling, represents an important step forward in this effort.1,2

Here’s how it works: The research team conjugates a protein-of-interest with a photocatalyst and then incubates the conjugate with cells in the presence of a biotin-labeled substrate of the photocatalyst. Then they expose the conjugate-cell mixture to visible light of a certain wavelength, which activates the photocatalyst, changing the substrate into a highly reactive molecular species. This molecule interacts with cell surface proteins in a residue-agnostic manner, biotinylating all proteins within a diameter of four nanometers. The team then enriches the biotinylated proteins with streptavidin and identifies the proteins using mass spectrometry.

In a July 2023 paper in Cell Chemical Biology from my team at Boston University, published in collaboration with Merck Exploratory Science Center, Cambridge, we modified the photo-proximity labeling technology for discovering cell surface proteins involved in the entry of SARS-CoV-2 into human cells.3 This ViraMap technology used the viral spike protein conjugated with an iridium-based photocatalyst. The subsequent enrichment of spike-interactors led to identification of novel SARS-CoV-2 entry factors, which we then validated by a number of orthogonal approaches.

Overall, this effort yielded new insights into how SARS-CoV-2 gains entry into various cells of the human body and causes the COVID-19 disease. The validation of ViraMap for the study of virus-cell surface interactions has opened doors for scientists and teams interested in using this technology to unravel the entry mechanisms for other medically-important viruses, paving the way for the development of effective antiviral therapeutics.

  1. Geri, J.B., Oakley, J.V., Reyes-Robles, T., Wang, T., McCarver, S.J., White, C.H., Rodriguez-Rivera, F.P., Parker, D.L., Jr., Hett, E.C., Fadeyi, O.O., et al. (2020). Microenvironment mapping via Dexter energy transfer on immune cells. Science 367, 1091-1097. 10.1126/science.aay4106.
  2. Ryu, K.A., Kaszuba, C.M., Bissonnette, N.B., Oslund, R.C., and Fadeyi, O.O. (2021). Interrogating biological systems using visible-light-powered catalysis. Nat Rev Chem 5, 322-337. 10.1038/s41570-021-00265-6.
  3. Datta, S., Chen, D.Y., Tavares, A.H., Reyes-Robles, T., Ryu, K.A., Khan, N., Bechtel, T.J., Bertoch, J.M., White, C.H., Hazuda, D.J., et al. (2023). High-resolution photocatalytic mapping of SARS-CoV-2 spike interactions on the cell surface. Cell Chem Biol. 10.1016/j.chembiol.2023.06.028.

Information For...