The Spike Protein of SARS-CoV-2 has been shown to interact with tumor suppressor p53. p53 mutations are the most common genetic alterations found in cancers and are observed in >50% of all tumors. From the approximately 200 different single mutations already described in p53, several residues are considered as hotspots, including R248, R175, G245, R273, R249, and R282 (Petitjean et al. 2007). All of these residues are found in p53's core domain, which is responsible for its interactions with DNA. For this reason, most of these mutants are incapable of exerting the wild-type (WT) level of transcriptional activity (Bullock et al. 1997). The most frequent effect of p53 mutations is loss-of-function (LoF); however, GoF effects, such as increased migration, invasion, and metastasis, have also been observed. Mutations in the p53 gene occur in more than half of human cancers and often result in altered transcriptional activities.