The activation of the VDES/VDR may yield positive effects against COVID-19, enhancing the antiviral response by boosting the production of antimicrobial peptides (AMPs) such as cathelicidin (cAMP/LL37) and β-defensin (DEFB4), as well as modulation–induction of viral autophagy and inhibition of the key Skp2 protein. Here, SKP2 is linked to COVID-19.