TP53 and cancer: In this study, we performed cell-based assays to examine the effect of SARS-CoV-2 on p53 activation in cancer cells and demonstrate that SARS-CoV-2 spike interrupts the MDM2-p53 interaction in cancer cells and alters p53 signaling in cancer cells upon chemotherapy including blunted activation of p53 targets involved in growth arrest and apoptosis.