Bovine lactoferrin suppresses the cathepsin-dependent pathway of SARS-CoV-2 entry in vitro

Kobayashi-Sakamoto et al., International Dairy Journal, doi:10.1016/j.idairyj.2023.105805

Sep 2023

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In Vitro study showing variant dependent inhibition of SARS-CoV-2 with bovine lactoferrin (bLF). Authors found that bLF did not suppress entry of wild-type pseudoviruses into cells that express both ACE2 and TMPRSS2, but did suppress entry of Omicron pseudoviruses. bLF suppressed entry of wild-type pseudoviruses into ACE2-expressing cells but not into TMPRSS2-expressing cells.

12 preclinical studies support the efficacy of lactoferrin for COVID-19:

2 In Silico studies Cutone, Miotto

9 In Vitro studies Alves, Andreu, Cutone, Kobayashi-Sakamoto, Mirabelli, Ostrov, Piacentini, Salaris, Yazawa

1 In Vivo animal study Berkowitz

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1. Alves et al., Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States, Pharmaceuticals, doi:10.3390/ph16101352.mdpi.com, doi.org.

2. Andreu et al., Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro, Viruses, doi:10.3390/v15040972.mdpi.com, doi.org.

3. Berkowitz et al., Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics, International Journal of Molecular Sciences, doi:10.3390/ijms242115718.mdpi.com, doi.org.

4. Cutone et al., Lactoferrin binding to Sars-CoV-2 Spike glycoprotein protects host from infection, inflammation and iron dysregulation., Research Square, doi:10.21203/rs.3.rs-1605740/v1.researchsquare.com, doi.org.

5. Kobayashi-Sakamoto et al., Bovine lactoferrin suppresses the cathepsin-dependent pathway of SARS-CoV-2 entry in vitro, International Dairy Journal, doi:10.1016/j.idairyj.2023.105805.sciencedirect.com, doi.org.

6. Miotto et al., Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin, Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2021.607443.frontiersin.org, doi.org.

7. Mirabelli et al., Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2105815118.pnas.org, doi.org.

8. Ostrov et al., Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells, Pathogens, doi:10.3390/pathogens10111514.mdpi.com, doi.org.

9. Piacentini et al., Lactoferrin Inhibition of the Complex Formation between ACE2 Receptor and SARS CoV-2 Recognition Binding Domain, International Journal of Molecular Sciences, doi:10.3390/ijms23105436.mdpi.com, doi.org.

10. Salaris et al., Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro, Nutrients, doi:10.3390/nu13020328.mdpi.com, doi.org.

11. Yazawa et al., Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19, Research Square, doi:10.21203/rs.3.rs-2676422/v1.researchsquare.com, doi.org.

Kobayashi-Sakamoto et al., 21 Sep 2023, peer-reviewed, 7 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

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