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.

Copper brain protein protection against free radical-induced neuronal death: Survival ratio in SH-SY5Y neuroblastoma cell cultures.

In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu+2 to cupreous Cu+. In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in ß-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects. With neuroblastoma SH-SY5Y cell cultures, we show that bovine brain prion protein in Cu but not Mn form prevents free radical-induced neuronal death. The survival ratio of SH-SY5Y cells has been measured after UV irradiation (free radical production), when the incubating medium is supplemented with bovine brain homogenate in native, Cu or Mn forms. This ratio, about 28% without any addition or with bovine brain protein added in Mn form, increases by as much as 54.73% with addition to the culture medium of native bovine brain protein and by as much as 95.95% if the addition is carried out in cupric form. This protective effect of brain copper protein against free radical-induced neuronal death has been confirmed with Inductively Coupled Plasma Mass Spectrometry Mn and Cu measurement in bovine brain homogenates: respectively lower than detection limit and 9.01µg/g dry weight for native form; lower than detection limit and 825.85µg/g dry weight for Cu-supplemented form and 1.75 and 68.1µg/g dry weight in Mn-supplemented brain homogenate.

Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob diseases the common key for a free radical mechanism and oxidative stress-induced damage?

In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases, similar pathological hallmarks have been described, one of which is brain deposition of abnormal protease-resistant proteins. For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a mechanism has been proposed that may underlie the neurodegenerative processes that occur when copper protection against free radicals is impaired. In peptide sequences, the alpha acid proton near the peptide bond is highly mobile and can be pulled out by free radicals. It will produce a trivalent α-carbon radical and induce a free radical chain process that will generate a D-amino acid configuration in the peptide sequence. Since only L-amino acids are physiologically present in mammalian (human) proteins, it may be supposed that only physiological L-peptides can be recycled by physiological enzymes such as proteases. If a D-amino acid is found in the peptide sequence subsequent to deficient copper protection against free radicals, it will not be recognized and might alter the proteasome L-amino acid recycling from brain peptides. In the brain, there will result an accumulation of abnormal protease-resistant proteins such as those observed in AD, LBD, and CJD.

If exposure to aluminium in antiperspirants presents health risks, its content should be reduced.

Since aluminium (Al) pervades our environment, the scientific community has for many years raised concerns regarding its safety in humans. Al is present in numerous cosmetics such as antiperspirants, lipsticks and sunscreens. Al chlorohydrate is the active antiperspirant agent in underarm cosmetics and may constitute for Al a key exposure route to the human body and a potential source of damage. An in vitro study has demonstrated that Al from antiperspirant can be absorbed through viable human stripped skin. The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate in the mammary gland and selectively interfere with the biological properties of breast epithelial cells, thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation. In addition, several studies suggest that the presence of Al in human breast could influence metastatic process. As a consequence, given that the toxicity of Al has been widely recognized and that it is not a physiological component in human tissues, reducing the concentration of this metal in antiperspirants is a matter of urgency.

Free radical generation of protease-resistant prion after substitution of manganese for copper in bovine brain homogenate.

The exchange between copper and seven transition metals is studied in a bovine brain obex homogenate according to the redox status of the medium. In reductive conditions, almost all the studied metals can substitute for copper when it is in the reduced form Cu+. This substitution is reversible, since copper uptake as Cu++ is restored in an oxidizing medium but only Co++, Ni++ and Mn++, in this decreasing order, can substitute perfectly for copper in bovine brain homogenate. To study free radical effects on bovine brain proteins, at first a copper substitution was processed in order to inhibit superoxide dismutase-like protective properties against free radicals in copper metalloproteins. Manganese was selected since a brain copper decrease correlated with a manganese increase is well-known in transmissible spongiform encephalopathies. Results for bovine brain homogenate, initially negative in the Western blot Prionics test, indicate that the substitution of manganese for copper in a reducing medium and exposure to UVA-induced free radicals produce proteinase K resistant prion. These findings suggest that an impairment in brain metal homeostasis leading to oxidative abnormalities may be involved in transmissible spongiform encephalopathies.

Aluminum L-glutamate complex in rat brain cortex: in vivo prevention of aluminum deposit by magnesium D-aspartate.

Our previous experiments in the rat showed that aluminum L-glutamate complex (Al L-Glu) crosses the blood-brain barrier and accumulates in selective brain areas and that Al salts may increase D-aspartic acid forms in living brain proteins, probably by inducing more thermodynamically stable structures than L isomers. As magnesium blocks NMDA receptors, D-aspartic acid was used in the present study in the form of magnesium salt to prevent the excitotoxicity of dicarboxylic amino acids. Effects on brain amino acids and Al cortex levels in mature rats were studied after chronic treatment with Al L-Glu or Na L-Glu alone or in association with magnesium D-aspartate (Mg D-Asp). Results demonstrate that treatment with Mg D-Asp induces a decrease in the Al concentration in brain cortex of Al L-Glu-treated rats. In aluminum-free treated controls, treatment with Mg D-Asp in association with Na L-Glu also induces a decrease in Al concentration in brain cortex. These data indicate that Mg D-Asp administration protects rat brain cortex from Al accumulation and suggest that this treatment may be useful in preventing brain Al intoxication.