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The challenges posed by emergent strains of SARS-CoV-2 need to be tackled by contemporary scientific approaches, with proteomics playing a significant role. In this review, we provide a brief synthesis of the impact of proteomics technologies in elucidating disease pathogenesis and classifiers for the prognosis of COVID-19 and propose proteomics methodologies that could play a crucial role in understanding emerging variants and their altered disease pathology. From aiding the design of novel drug candidates to facilitating the identification of T cell vaccine targets, we have discussed the impact of proteomics methods in COVID-19 research. Techniques varied as mass spectrometry, single-cell proteomics, multiplexed ELISA arrays, high-density proteome arrays, surface plasmon resonance, immunopeptidomics, and  in silico  docking studies that have helped augment the fight against existing diseases were useful in preparing us to tackle SARS-CoV-2 variants. We also propose an action plan for a pipeline to combat emerging pandemics using proteomics technology by adopting uniform standard operating procedures and unified data analysis paradigms. The knowledge about the use of diverse proteomics approaches for COVID-19 investigation will provide a framework for future basic research, better infectious disease prevention strategies, improved diagnostics, and targeted therapeutics.

Rise of the SARS-CoV-2 Variants: can proteomics be the silver bullet?