Pharmaceuticals (Aug 2024)

Lactoferrin Binds through Its N-Terminus to the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

  • Patrik Babulic,
  • Ondrej Cehlar,
  • Gabriela Ondrovičová,
  • Tetiana Moskalets,
  • Rostislav Skrabana,
  • Vladimir Leksa

DOI
https://doi.org/10.3390/ph17081021
Journal volume & issue
Vol. 17, no. 8
p. 1021

Abstract

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Since Coronavirus disease 2019 (COVID-19) still presents a considerable threat, it is beneficial to provide therapeutic supplements against it. In this respect, glycoprotein lactoferrin (LF) and lactoferricin (LFC), a natural bioactive peptide yielded upon digestion from the N-terminus of LF, are of utmost interest, since both have been shown to reduce infections of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, in particular via blockade of the virus priming and binding. Here, we, by means of biochemical and biophysical methods, reveal that LF directly binds to the S-protein of SARS-CoV-2. We determined thermodynamic and kinetic characteristics of the complex formation and mapped the mutual binding sites involved in this interaction, namely the N-terminal region of LF and the receptor-binding domain of the S-protein (RBD). These results may not only explain many of the observed protective effects of LF and LFC in SARS-CoV-2 infection but may also be instrumental in proposing potent and cost-effective supplemental tools in the management of COVID-19.

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