Targeting ATP2B1 impairs PI3K/Akt/Forkhead box (Fox) transcription factor signaling and reduces SARS-COV-2 infection and replication

RNA-seq of human cells Edited using CRISPR vs parental and Unedited control. We identified a rare homozygous intronic variant in the ATP2B1 locus (rs111337717; chr12:89643729, T>C) that is associated with the severity of COVID-19 (i.e., symptomatic versus asymptomatic patients). Next, we employed CRISPR/Cas9 technology to develop the disease mutation observed in high-risk patients. Several edited single colonies were picked and expanded followed by DNA sequencing, and four clones with desired homozygous modifications were identified. The transcriptional profiles of N=4 C/C clones were compared then to those of T/T controls comprising one parental cell line and three unedited post-selection HEK293T cell clones.