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Lactoferrin binding to Sars-CoV-2 Spike glycoprotein protects host from infection, inflammation and iron dysregulation.

Cutone et al., Research Square, doi:10.21203/
May 2022  
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Vero E6, Caco-2, and THP-1 In Vitro study showing lactoferrin inhibited SARS-CoV-2 spike pseudovirus. Nutraceutically available bovine lactoferrin was more effective than human lactoferrin.
Cutone et al., 17 May 2022, Italy, preprint, 12 authors. Contact:
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperLactoferrinAll
Lactoferrin binding to Sars-CoV-2 Spike glycoprotein protects host from infection, inflammation and iron dysregulation.
Antimo Cutone, Luigi Rosa, Maria Carmela Bonaccorsi Di Patti, Federico Iacovelli, Maria Pia Conte, Giusi Ianiro, Alice Romeo, Elena Campione, Luca Bianchi, Piera Valenti, Mattia Falconi, Giovanni Musci
The anti-SARS-Cov-2 activity of the iron-binding protein Lactoferrrin has been investigated in epithelial and macrophagic cell models using a Pseudovirus decorated with the SARS-CoV-2 Spike glycoprotein. The human and, even more, the nutraceutically available bovine Lactoferrin inhibit pseudoviral infection in all cellular models tested. The bovine protein efficiently counteracts the deleterious effects of purified Spike on iron and inflammatory homeostasis, as shown by restored levels of the main proteins of the iron-handling system and, in the case of macrophagic THP-1 cells, of the proinflammatory cytokines IL-1β and IL-6. A direct interaction between Lactoferrin and Spike is likely at the basis of the observed effects, as demonstrated by an in vitro pull-down assay. Finally, in silico approaches have been applied to analyze the interactions of human and bovine Lactoferrins with Transferrin Receptor 1, a potential gate for SARS-CoV-2 entry into cells, as well as the binding of the bovine protein to different variants of concern of the SARS-Cov-2 Spike glycoprotein. Our results give hope for the employment of bovine Lactoferrin as an adjuvant of the standard of care therapies in COVID-19 treatment.
Statements and Declarations Competing Interests No competing interests do declare. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by all authors. The first draft of the manuscript was written by Antimo Cutone, Luigi Rosa and Mattia Falconi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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