Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balanced membrane-attached and free circulating ACE2 and between angiotensin II and angiotensin (1–7) (Ang-(1–7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming. The gene discussed is AGT; the disease is obesity due to melanocortin 4 receptor deficiency.