A New Inactivation Method to Facilitate Cryo-EM of Enveloped, RNA Viruses Requiring High Containment: A Case Study using Venezuelan Equine Encephalitis Virus (VEEV).

•A rapid and simple method to inactivate and purify enveloped RNA viruses for cryo-EM requiring BSL-3 containment is demonstrated.•Using VEEV TC-83 as a test case, a cryo-EM map of fixed, inactivated VEEV was determined to a resolution of 7.9 Å.•Features like icosahedral symmetry, capsid organization and trimeric spikes in our map were similar to the map of the native virus.•Our methodology can be adapted for other enveloped, RNA viruses requiring high containment.