Lactoferrin Inhibition of the Complex Formation between ACE2 Receptor and SARS CoV-2 Recognition Binding Domain
Roberta Piacentini, Laura Centi, Mattia Miotto, Edoardo Milanetti, Lorenzo Di Rienzo, Martina Pitea, Paolo Piazza, Giancarlo Ruocco, Alberto Boffi, Giacomo Parisi
International Journal of Molecular Sciences, doi:10.3390/ijms23105436
The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum "physiological" lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD-ACE2 binding, bringing about a measurable, up to 300-fold increase of the K D value relative to RBD-ACE2 complex formation.
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'abstract': '<jats:p>The present investigation focuses on the analysis of the interactions among human '
'lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting '
'enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a '
'molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. '
'In particular, kinetic and thermodynamic parameters for the pairwise interactions among the '
'three proteins were measured via two independent techniques, biolayer interferometry and '
'latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is '
'able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no '
'binding to the RBD was observed up to the maximum “physiological” lactoferrin concentration '
'range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with '
'RBD–ACE2 binding, bringing about a measurable, up to 300-fold increase of the KD value '
'relative to RBD–ACE2 complex formation.</jats:p>',
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