AKT1 and Insulin resistance: Host factors further rewire this axis: SARS-CoV-2 proteins perturb IRS adaptors and upregulate suppressor of cytokine signaling-3, blunting Akt and contributing to de novo insulin resistance (human mechanistic/observational), while estrogen receptor-α scaffolds IRS-1 to bolster Akt–mTORC2 (mechanistic; sex-difference context) (128, 129).