###### Abstract  
We introduce a magnetic bead-based sample preparation scheme for enabling the Raman spectroscopic differentiation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-positive and -negative samples. The beads were functionalized with the angiotensin-converting enzyme 2 (ACE2) receptor protein, which is used as a recognition element to selectively enrich SARS-CoV-2 on the surface of the magnetic beads. The subsequent Raman measurements directly enable discriminating SARS-CoV-2-positive and -negative samples. The proposed approach is also applicable for other virus species when the specific recognition element is exchanged. A series of Raman spectra were measured on three types of samples, namely SARS-CoV-2, Influenza A HIN1 virus and a negative control. For each sample type, eight independent replicates were considered. All of the spectra are dominated by the magnetic bead substrate and no obvious differences between the sample types are apparent. In order to address the subtle differences in the spectra, we calculated different correlation coefficients, namely the Pearson coefficient and the Normalized cross correlation coefficient. By comparing the correlation with the negative control, differentiating between SARS-CoV-2 and Influenza A virus is possible. This study provides a first step towards the detection and potential classification of different viruses with the use of conventional Raman spectroscopy. viruses; SARS-CoV-2; Raman spectroscopy; magnetic beads; sample preparation 2023 13 594 02023 02023 02023 02023 02023 02023 02023 02023 02023 02023 02023 023 are fast, highly adaptable and can successfully diversify through random and frequently occurring mutations and recombination [3]. The recent Corona Virus Disease 2019 (COVID-19) pandemic has again illustrated how fast and devastating the outcome of a zoonotic virus can be as it jumped across the species barrier [4]. Unfortunately, such crossings of the species barriers occur quite frequently and are a natural phenomenon. Modern life style changes, globalization and the destruction of natural environments promote the occurrence of such events because they lead to more intense contact between humans and different carriers of potentially infectious viruses [5]. Accordingly, the emergence of highly contagious viruses is a constant threat and scientists warn constantly that even worse scenarios are likely in the future. Continuous research aiming for the development of rapid, fast, economic, adaptable, specific, sensitive and simple diagnostic assays, together with antiviral drugs and vaccines, are key components for the preparation for, and prevention of, future outbreaks and for limiting the subsequent damage. The current gold standard for enabling high specificity and sensitivity for diagnosing viral infections are Polymerase Chain Reaction (PCR)-based methods, including RT-PCR (reverse transcription PCR), by which the virus species or strains are identified according to characteristic nucleic acid sequences [6; 7]. Despite these important advantages and their widespread application, there are some drawbacks that should not be overlooked. To date, PCR assays have remained expensive and require specialized laboratory settings with trained personnel and infrastructure. Especially in cases of a pandemic, it is crucial to consider that a global surveillance strategy, which is applicable with minimal resources, is needed. Lateral flow tests are a simple and fast detection method. Unfortunately, the sensitivity of such tests is usually considerably lower compared to PCR-based methods [8]. This highlights the need for the development of low cost and simple technologies with the potential to be applied in a decentralized way. Spectroscopic methods appear to be a promising option as they are fast, applicable on site and give access to a wealth of information on the sample of interest. Raman spectroscopy is highly specific in terms of probing the molecular structure.