The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.g., dedicated personnel and short-term activity), have become issues at the forefront of public health concerns. This issue became especially pressing when infection-mitigating supplies dwindled early in the progression of the pandemic. In consideration of the constant threat posed by emerging novel viruses, we report a platform technology for persistent surface disinfection to combat virus transmission through nanomaterial-mediated, localized UV radiation emission. In this work, two formulations of Y2SiO5-based visible-to-UV upconversion nanomaterials were developed using a facile sol-gel-based synthesis. Our formulations have shown substantial antiviral activities (4 x 10(4) to 0 TCID50 units in 30 min) toward an enveloped, circulating human coronavirus strain (OC43) under simple white light exposure as an analogue to natural light or common indoor lighting. Additionally, we have shown that our two formulations greatly reduce OC43 RNA recovery from surfaces. Antiviral activities were further demonstrated toward a panel of structurally diverse viruses including enveloped viruses, SARS-CoV-2, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, and Zika virus, as well as nonenveloped viruses, rhinovirus, and calicivirus, as evidence of the technology\'s broad antiviral activity. Remarkably, one formulation completely inactivated 10(5) infectious units of SARS-CoV-2 in only 45 min. The detailed technology has implications for the design of more potent, long-lived disinfectants and modified/surface-treated personal protective equipment targeting a wide range of viruses.