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Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The frequent appearance of variants requires adjunct strategies to combat SARS-CoV-2 infections. Lactoferrin, a naturally occurring glycoprotein, exhibits promising antiviral properties. Here, we investigated the efficacy of bovine LF (bLF) against SARS-CoV-2 infection. SARS-CoV-2 pseudoviruses bearing the original Wuhan (wild-type), D614G mutant, or Omicron variant spike proteins were used to examine the effects of bLF on viral entry into host cells. We found that although bLF did not suppress entry of wild-type pseudoviruses into cells expressing both human angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), it did suppress entry of Omicron pseudoviruses into the cells. The results of this in vitro study highlight the spike protein-dependent effects of bLF on suppression of pseudovirus entry into host cells. Future clinical trials investigating the efficacy of bLF against SARS-CoV-2 infection should consider the differential impact of virus variants. [ABSTRACT FROM AUTHOR]

COVID-19 is a devastating pandemic responsible for the current global health crisis. Hyperimmune milk, produced after maternal immunisation of bovines, equines, camels, sheep, goats and humans, may act as a super food since it possesses strong nutritional, health promoting, antiviral and immunomodulating properties. It may also be a good and instantaneous source of passive immunity against COVID-19 via bioactive factors, viz., IgG, IgA and IgM neutralising antibodies. The modularity of these antibodies makes them amenable to neutralise SARS-CoV-2 by agglutination and complement fixation in addition to inhibition of various metabolic enzymes. Due to unique nutritional configuration and presence of variable antigen-binding domains, hyperimmune camel milk also possesses potential for induction of passive immunity by the development of multivalent complexes against SARS-CoV-2. Being almost devoid of SARS-CoV-2 RNA, and after thorough investigation, high-pressure pasteurised hyperimmune milk can be safely recommended in the human diet especially for immunocompromised patients and non-vaccinated children. [ABSTRACT FROM AUTHOR]

The entry of SARS-CoV-2 into host cells may involve the spike protein cleavage by cathepsin L (CTSL). Certain food proteins such as lactoferrin (Lf) inhibit CTSL. The current study investigated the impact of hydrolysis (0–180 min) by proteinase K on electrophoretic pattern, secondary structure, cathepsin inhibitory and SARS-CoV-2 pseudovirus infectivity inhibitory of bovine Lf. Gel electrophoresis indicated that hydrolysis cut Lf molecules to half lobes (∼40 kDa) and produced peptides ≤18 kDa. Approximation of the secondary structural features through analysis of the second-derivative amide I band collected by infra-red spectroscopy suggested a correlative–causative relationship between cathepsin inhibition and the content of helix-unordered structures in Lf hydrolysate. The half maximal inhibitory concentration (IC 50) of Lf hydrolysed for 90 min (H90) against CTSL was about 100 times smaller than that of the Lf hydrolysed for 0 min (H0). H90 had also double activity against SARS-CoV-2 pseudo-types infectivity compared with H0. [ABSTRACT FROM AUTHOR]

Bovine whey IgG enriched fraction contains IgG antibodies against bacterial and viral pathogens, including antibodies against the spike protein [amino acids (aa) 1–1274] of SARS-CoV-2 Wuhan strain (2019-nCoV WHU01). To date, 13 SARS-CoV-2 variants have been identified, including gamma, delta, kappa, and omicron, which contain 10, eight, seven, and over 30 mutations in the spike protein, respectively. We investigated whether bovine whey IgG enriched fraction contains antibodies against spike proteins of these variants, specifically recombinant partial length spike proteins (aa 177–512, aa 509–685, aa 177–324, aa 250–410 and aa 387–516) of these variants. Direct enzyme-linked immunosorbent assays revealed bovine whey IgG enriched fraction contained antibodies against all recombinant spike proteins of these variants with highest reactivity against aa 177–512 region of omicron spike protein. These results indicate bovine whey IgG enriched fraction contains antibodies against spike proteins of several SARS-CoV-2 variants, including omicron. [ABSTRACT FROM AUTHOR]

Bovine whey IgG enriched fraction contains antibodies against various human bacterial pathogens. It contains antibodies against some viral antigens, including human respiratory syncytial virus and influenza virus. We investigated whether the IgG enriched fraction has cross-reactivity with IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. The full-length and partial-length SARS-CoV-2 S, N, a recombinant protein of the receptor binding domain (RBD) and nine peptides covering the receptor binding motif (RBM) of S were prepared. Direct enzyme-linked immunosorbent assays were conducted using these recombinant proteins and peptides as coating antigens and revealed the IgG enriched fraction contained antibodies against partial-length S [amino acids (aa) 177–512, 288–512, 348–578, 387–516 and 408–664], full-length N (aa 1–419) and partial-length N (aa 1–120, 111–220, 1–220 and 210–419), two RBD peptides, covering aa 427–446 and 502–520 of S, and recombinant RBD of S. These results indicate IgG enriched fraction contains antibodies against SARS-CoV-2. [ABSTRACT FROM AUTHOR]