Lastly, rSARS-CoV-2N4A infection of A549-ACE2 cells led to a higher induction of a canonical ISG, MX1, than infection with rSARS-CoV-2WT (Fig. 6F); this observation could be a result of altering the viral gene ORF9B that overlaps with N. In summary, we found that ablation of the phosphorylation of N-terminal N residues inhibited viral production, albeit less significantly than genetic inhibition of p38β, suggesting that p38 impacts viral replication by modulating both viral and host substrates. Here, MAPK11 is linked to infection.