APOBEC cellular enzymes as 'court jesters' in SARS-CoV-2 evolution.

Human cellular APOBEC enzymes were largely reported as involved in innate antiviral defenses. We previously highlighted that in SARS-CoV-2 genomes obtained in our center, nearly half of 'hyperfertile' or 'fertile' mutations while 23% of neutral/weakly deleterious mutations had APOBEC signatures. Here we determined that 29% of mutations we named 'lethal' as detected in quasispecies but not in consensus genomes have APOBEC signatures. Overall, these results do not suggest that human APOBEC acts as defense agents against SARS-CoV-2 but as 'Court Jesters', being neither friends nor foes but only enzymes whose activity can either favor or hamper viral fitness according to the Kimura theory of neutral evolution.