Proteotypic peptides for SARS-CoV-2 variant detection

The recent SARS-CoV-2 omicron variant presented significant challenges to the global effort to counter the pandemic. SARS-CoV-2 is predicted to remain prevalent in the coming months, making the ability to identify SARS-CoV-2 variants imperative in understanding and controlling the pandemic. The predominant variant discovery method, genome sequencing, is time-consuming, insensitive, and expensive. Liquid chromatography-mass spectrometry (LC-MS) offers an exciting alternative detection modality provided that variant-containing peptide markers become well-established. This study demonstrates the potential to establish SARS-CoV-2 peptide markers by examining amino-acid variant-containing tryptic peptides, their MS fragmentation intensities, and their detection sensitivity in MS experiments. We have synthesized model tryptic peptides from of SARS-CoV-2 variants beta, gamma, delta, and omicron and evaluated their signal intensity, HCD spectra, and reverse phase retention time.