Copper acetate aerosols: A possible tool complementary to vaccination in fight against SARS-CoV-2 and variants replication.

In SARS-CoV-2, at the S1/S2 furin cleavage site, a four amino acid insert (P-R-R-A) not found in closely related corona viruses, has been shown to facilitate entry into respiratory epithelial cells and promote virus transmission, infectivity and virulence. By cupric aerosol treatment, complexation of these four amino acids (-P-R-R-A-), at the spike (S) protein site will lead to a conformational change possibly impeding SARS-CoV-2 replication process in the respiratory track. Since these four amino acids yield strong and stable copper complexes, subsequent to a steric hindrance, this complexation will disturb the furin-like protease cleavage at the spike protein site as it has been recently shown in vitro with copper gluconate. The compilation of stability constants for copper amino-acid complex formation, showing values of the same order of magnitude for all the twenty proteinogenic amino-acids demonstrate thermodynamically that copper amino-acid chelation for SARS-CoV-2 virus will not be affected by mutations leading to amino acid exchanges in the spike protein region. Given its low toxicity, and its very low stability formation constant, copper acetate is proposed rather than copper gluconate for possible cupric aerosol or nasal spray treatments aimed at impeding SARS-CoV-2 multiplication. It will open different medical perspectives, complementary to vaccination, in the fight against COVID 19 native virus, variants and future mutants.