Many events in viral infection are regulated through post-translational modification. In the case of positive-sense RNA viruses such as SARS-CoV-2 which encodes two viral proteases, proteolytic cleavage of both viral and cellular proteins is crucial for productive viral infection. In this work we study proteolysis in the context of SARS-CoV-2 infection of Vero E6 cells, treated with calpeptin or camostat at 12h post-infection and harvested at 24h post-infection. Our goal was Neo-N-termini and lysine residues were labelled at the protein level with TMTpro reagents prior to tryptic digestion. For unenriched samples, the trypsin-digested material was then fractionated offline, and analysed by LC-MS/MS for the study of total protein abundance over the infection timecourse. For enriched samples, unblocked neo-N-termini generated by tryptic digested were labelled with undecanal and depleted, yielding a sample enriched for blocked neo-N-termini (TMTpro, N-terminal acetylation, and pyroGlu). The enriched samples were similarly fractionated offline and analysed by LC-MS/MS.