PT - JOURNAL ARTICLE AU - George Devitt AU - Peter B. Johnson AU - Niall Hanrahan AU - Simon I.R. Lane AU - Magdalena C. Vidale AU - Bhavwanti Sheth AU - Joel D. Allen AU - Maria V. Humbert AU - Cosma M. Spalluto AU - Rodolphe C. Hervé AU - Karl Staples AU - Jonathan J. West AU - Robert Forster AU - Nullin Divecha AU - Christopher J McCormick AU - Max Crispin AU - Nils Hempler AU - Graeme P. A. Malcolm AU - Sumeet Mahajan TI - Mechanisms of SARS-CoV-2 Inactivation using UVC Laser Radiation AID - 10.1101/2023.02.03.526944 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.02.03.526944 4099 - http://biorxiv.org/content/early/2023/02/03/2023.02.03.526944.short 4100 - http://biorxiv.org/content/early/2023/02/03/2023.02.03.526944.full AB - Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50mJ/cm2 using a UVC laser at 266nm achieved an inactivation efficiency of 99.89%, whilst infectious virions were undetectable at 75mJ/cm2 indicating >99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterisation of UVC-induced damage of the S protein. We find that UVC severely impacts SARS-CoV-2 spike protein’s ability to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.Competing Interest StatementThe authors have declared no competing interest.