(1) Background: Angiotensin-converting enzyme 2 (ACE2) is a crucial functional receptor of the SARS-CoV-2 virus. Although the scale of infections is no longer at pandemic levels, there are still fatal cases. The potential of the virus to infect the skin raises questions about new preventive measures. In the context of anti-SARS-CoV-2 applications, the interactions of antimicrobial nanomaterials (silver, Ag; diamond, D; graphene oxide, GO and their complexes) were examined to assess their ability to affect whether ACE2 binds with the virus. (2) Methods: ACE2 inhibition competitive tests and in vitro treatments of primary human adult epidermal keratinocytes (HEKa) and primary human adult dermal fibroblasts (HDFa) were performed to assess the blocking capacity of nanomaterials/nanocomplexes and their toxicity to cells. (3) Results: The nanocomplexes exerted a synergistic effect compared to individual nanomaterials. HEKa cells were more sensitive than HDFa cells to Ag treatments and high concentrations of GO. Cytotoxic effects were not observed with D. In the complexes, both carbonic nanomaterials had a soothing effect against Ag. (4) Conclusions: The Ag5D10 and Ag5GO10 nanocomplexes seem to be most effective and safe for skin applications to combat SARS-CoV-2 infection by blocking ACE2-S binding. These nanocomplexes should be evaluated through prolonged in vivo exposure. The expected low specificity enables wider applications.
