The Rapid‑Corona project, carried out from 1 February 2021 to 30 June 2023, aimed to create a rapid, oral‑based sensor that detects SARS‑CoV‑2 infection by responding to virus‑specific proteases present in human saliva. The core concept relies on short peptide substrates that are cleaved by selected viral or host proteases, producing a visible or taste change that signals infection.

The technical work began with a comprehensive proteomic analysis of saliva samples to identify suitable target proteases. Initial literature screening highlighted furin and the transmembrane serine protease 2 (TMPRSS2) as promising candidates because of their established roles in viral entry. During the project, three additional proteases were incorporated: the viral main protease (Mpro), the papain‑like protease (PLpro), and proteinase 3 (PR3). This expansion required a revision of the original work packages but was successfully completed.

Using the protease‑informed cleavage sequencing (PICS) workflow, the team identified and characterized cleavage motifs for each protease. The resulting peptide sequences were synthesized and tested for specificity and sensitivity. Three peptide‑based sensors were produced, each tailored to one of the proteases. One of the sensors displayed insufficient selectivity and was discarded, leaving two robust sensors. These were combined into a multiplexing system that can simultaneously monitor multiple protease activities. Ex‑vivo experiments with cultured SARS‑CoV‑2 and viral supernatants confirmed that the multiplexed sensor set could detect viral presence, demonstrating functional proof of concept.

The sensors were further integrated into an oral thin‑film format, a platform already produced by one of the consortium partners under GMP conditions. This step is essential for translating the laboratory prototype into a user‑friendly diagnostic tool that could be swallowed or chewed, offering a non‑invasive alternative to nasopharyngeal swabs. While the report does not provide quantitative performance metrics such as limit of detection or kinetic parameters, it reports successful synthesis, characterization, and ex‑vivo validation of the sensor system.

Collaboration was central to the project’s success. The lead institution, Julius‑Maximilians‑University Würzburg, provided expertise in pharmaceutical technology and biopharmacy, as well as the core laboratory for peptide synthesis and sensor testing. The University’s clinical partners, the Department of Otolaryngology‑Head and Neck Surgery and the Department of Oral, Maxillofacial and Plastic Surgery, supplied patient saliva samples and clinical expertise in sample collection and virological analysis. 3a‑diagnostics GmbH contributed its experience in manufacturing oral thin films and chewing gum under GMP standards, enabling the rapid translation of the sensor into a consumable format. The project was coordinated by Prof. Dr. Dr. Lorenz Meinel, who served as the principal investigator and corresponding author.

The consortium’s work culminated in a set of manuscripts that will be submitted to peer‑reviewed journals. One manuscript will focus on furin‑responsive sensors for head‑and‑neck cancer, while another will detail the SARS‑CoV‑2‑specific PRTN3 and Mpro sensors, covering both methodology and the ex‑vivo results. The Rapid‑Corona project demonstrates a multidisciplinary approach to developing a rapid, saliva‑based diagnostic that could complement existing testing strategies during pandemics.