The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic required rapid in vitro diagnostic assay creation and scale-up. Global testing demand has strained the supply chain of reagents used in the molecular testing workflow for COVID-19. One bottleneck has been the supply of reagents used to extract and purify viral RNA from clinical specimens for subsequent RT-qPCR assays. To help alleviate this, Promega developed the XpressAmp™ Direct Amplification Reagents (Cat.# A8880, A8882) to provide a fast, RNA extraction-free method to prepare viral samples for PCR-based amplification. Preparing an infectious sample requires reagents that safely inactivate viral particles, thereby simplifying the laboratory process. This report describes an evaluation of the ability of the XpressAmp™ Lysis Buffer, used to prepare viral sample for RT-qPCR analysis, to inactivate the SARS-CoV-2 virus.