Figure 2.

Overview of antioxidant-dependent and -independent mechanisms used by melatonin to regulate m⁶A modifications during SARS-CoV-2 infection and PASC. Melatonin increases the m⁶A “reader” YTHDF2, allowing the proper nucleation of stress granules by G3BP1 to promote antiviral immune response. Melatonin inhibits GSK-3 gene expression and phosphorylation to suppress Gle1A hyperphosphorylation that allows DEAD-box RNA helicase DDX3X to interact with ALKBH5 and stress granules to enhance immune response that reduces viral transcription and replication. The suppression of GSK-3 increases the m⁶A demethylase FTO that “erases” modifications by m⁶A methyltransferase METTL3, decreasing m⁶A levels to suppress viral replication (see Abbreviations for additional acronyms).