Montana is a state with large rural and Tribal Nations populations. Both groups have been underrepresented in whole genome sequencing of SARS-CoV-2 variants and the state of Montana lags significantly behind the country as a whole in sequencing data available from patients infected with SARS-CoV-2. Given the emergence of dangerous SARS-CoV-2 variants with higher viral transmissibility and reduced response to monoclonal antibody therapy and vaccine efficacy, lack of sequencing data is a critical problem for the Montana state Department of Public Health and Human Services (DPHHS) in mounting an appropriate response to the pandemic. Furthermore, sequencing data will be particularly important for understanding viral transmission in Tribal Nations, which have been disproportionately affected by the pandemic. This supplement to the Center for Biomolecular Structure and Dynamics COBRE grant will allow whole genome sequencing and analysis of >3000 SARS-CoV-2 viruses isolated from patients in the state of Montana, including those living in rural and Tribal communities. General sequencing results will be made publicly available, except Tribal samples unless Tribal approval is given, through GenBank and GISAID to facilitate broader analysis of the emergence of variants of concern (VOC) and variants of interest (VOI) in the United States and will be communicated directly to the Montana DPHHS and participating Tribal Nations so that they can adjust their responses to the pandemic. We take advantage of the CLIA-certified SARS-CoV-2 testing facility on the University of Montana campus, our expertise in whole genome sequencing and our established relationships with Tribal Nations in Montana to accomplish the goals of this SARS-CoV-2 sequencing supplement. The analysis of these data will focus on three specific aims:  Specific Aim 1: What is the genetic structure of SARS-CoV-2 variants across Montana communities and how does this variation compare to regional, national, and global SARS-CoV-2 diversity?  Specific Aim 2: Does the genetic composition of circulating SARS-CoV-2 variants differ between rural versus metropolitan and Tribal versus non-Tribal communities in Montana?  Specific Aim 3: Are specific outbreaks associated with known or putative novel variants of interest and/or concern? Overall, the project will provide critical new insight into how more dangerous variants of SARS-CoV-2 arise and spread in a rural state and among the disproportionately-effected Tribal Nations in Montana that will allow for better response to the pandemic for these groups. This supplement to the Center for Biomolecular Structure and Dynamics COBRE grant will allow whole genome sequencing of SARS-CoV-2 viruses isolated from patients in the state of Montana. The results will permit tracking of the emergence of variants of concern in Montana allowing the state Department of Public Health and Human Services to better respond to the SARS-CoV-2 pandemic. The project also will address the deficiency in SARS-CoV-2 sequencing data in Montana and in particular for its rural and Tribal Nations populations.