Applications of Raman Spectroscopy in Pandemic Virology: A Comprehensive Review

Raman spectroscopy, with its ability to provide molecular fingerprinting of biological samples, has recently emerged as a powerful technique in virology. Unfortunately, emerging and re-emerging viral pathogens with a rising threat highlight the urgent requirementforrapid,sensitive,andlabel-freediagnostictoolstomonitorbothviralpresence and host responses. Recently, Raman spectroscopy use has increased not only in non pandemic viruses but also in pandemic-prone viruses. This review presents a comprehensive analysis of Raman spectroscopy and its enhanced variants, such as surface enhanced Raman spectroscopy (SERS), tip-enhanced Raman spectroscopy (TERS), and coherent Raman spectroscopies(CARS/SRS), in the context of pandemic virus research. By improving sensitivity, spatial resolution, and acquisition speed, these variants allow for quick and, in some cases, real-time analysis of viral particles and virus-host interactions in clinical samples and infected cells. A systematic evaluation of Raman-based methodologies was conducted across several virus families with pandemic potential, including Orthomyxoviridae, Coronaviridae, Filoviridae, Flaviviridae, and others, selected for their roles in past pandemics. Furthermore, prominent technical and virological obstacles hindering the expanded application of these methods were identified, alongside a discussion of prospective future directions for research and development. This effort aims to consolidate the current status of Raman spectroscopy in pandemic virology to enhance its integration into worldwide research on pandemic virus surveillance, pathogenesis, and diagnostics.