NIAID scientists have developed plasmids that allow for production of pseudoviruses expressing SARS-CoV-2 spike protein. As SARS-CoV-2 is a lethal airborne virus, it must be handled in high-containment Biosafety Level 3 (BSL-3) laboratories that require strict airflow, ventilation and decontamination procedures. The pseudotyping plasmids of this invention provide a secure platform for exploring SARS-CoV-2 dynamics without the need for high-risk handling of live virus and ensure a controlled environment for scientists to study SARS-CoV-2 more expeditiously in standard Biosafety Level 2 (BSL -2) laboratories. The plasmids can be used for diverse SARS-CoV-2 research applications, including the study of newly emerging or potential future variants of interest.