Inhibitory effect of whey protein concentrate on SARS‐CoV‐2‐targeted furin activity and spike protein‐ACE2 binding in methotrexate‐induced lung damage

Abstract

This study aims to investigate the effects of whey proteins on SARS CoV‐2 in methotrexate‐induced lung tissue damage in rats. To determine the possible effects, rats were divided into four groups as control, control + whey, methotrexate (20 mg/kg, i.p.) and methotrexate + whey. Whey protein concentrate (2 g/kg, oral gavage) was administered for 10 days. Cytokine levels were measured and protein electrophoresis was carried out in serum samples. Lipid peroxidation, nitric oxide and glutathione level, and superoxide dismutase and glutathione S transferase activities were determined in lung samples. Inhibition of SARS CoV‐2‐targeted lung furin activity and SARS CoV‐2 spike protein‐angiotensin converting enzyme binding with whey protein concentrate were also measured in each group. In conclusion, whey protein concentrate improved methotrexate‐induced lung damage and inhibited lung furin activity targeting SARS‐CoV‐2 S1/S2 site cleavage and SARS CoV‐2 spike protein‐angiotensin converting enzyme binding. Whey proteins are potential protective candidates that inhibit SARS CoV‐2‐related interactions, even in methotrexate‐induced lung injury. Practical applications Whey proteins have anticarcinogenic, antihypertensive, antioxidant, antibacterial, antiviral, and immunomodulating properties due to the protein, bioactive peptide, and essential amino acid content. Methotrexate is a folate antagonist and inhibits cell proliferation and purine synthesis. The combined use of whey protein concentrate and methotrexate may be an alternative in the development of new strategies to the treatment approaches against COVID‐19. In addition, according to the results of this study, it is thought that the protective effect of whey proteins in healthy conditions before encountering the SARS CoV‐2 may be higher than those who have never used it.

Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

“…Enhancing GSH, mainly through NAC, GSH precursors or pro-GSH compound administration, becomes a potential treatment option for SARS-CoV-2 infection and COVID-19 disease by reducing oxidative stress and cytokine expression especially in diabetic patients at risk of more severe disease ( Singh et al, 2022 ). Whey protein concentrate ameliorates lung damage and inhibits lung furin activity targeting SARS-CoV-2 S1/S2 site cleavage and SARS CoV-2 spike protein-angiotensin converting enzyme binding and could be used to protect against COVID-19 inhibiting SARS-CoV-2 cell entry ( Tufan et al, 2022 ). A combination of vitamin D and L-cysteine administration significantly augmented GSH levels and lowered oxidative stress and inflammation ( Jain et al, 2018 ; Jain and Parsanathan, 2020 ).…”

Preventative and therapeutic potential of animal milk components against COVID‐19: A comprehensive review

“…Whey peptides (4–13 residues) isolated from buffalo milk and colostrum have also been reported to show antiviral activity against SARS‐CoV‐2 in various ways, that is, inhibiting replication transcription complex, virion assembly, and endosomal maturation in addition to blocking viral entrance by binding to spike S and ACE2 (Pradeep et al, 2021 ). Recently Tufan et al ( 2022 ) reported that administration of WPC at the dose rate of 2 g/kg for 10 days reduced the oxidative lung injury caused by methotrexate and prevented lung furin activity and the binding of SARS‐CoV‐2 spike protein to ACE2 receptors. Different whey‐derived peptides, that is, “IPP,” “IIAE,” “LIVTQ,” and “LVYPFP,” may inhibit SARS‐CoV‐2 entrance by suppressing ACE2 through precise molecular interactions with important ACE2 residues (Chamata et al, 2021 ).…”

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

“…GSH dysregulation might cause global immune cell autophagy decline with increased generation of proinflammatory cytokines in aging, further provoked by mitochondrial ROS signaling (293). Whey protein concentrate ameliorates lung damage and inhibits lung furin activity targeting SARS-CoV-2 S1/S2 site cleavage and SARS CoV-2 spike protein-angiotensin converting enzyme binding and could be used to protect against COVID-19 inhibiting SARS-CoV-2 cell entry (300). Glutamine, glycine, N-acetylcysteine, selenium, whey protein isolates with bonded cysteine, GSH and pro-GSH supplementation improves GSH deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, cognition and surfactant regeneration (301)(302)(303)(304)(305)(306)(307).…”