The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria.

Etheresia Pretorius,Eugene L Heyden,Douglas B Kell

doi:10.3389/fimmu.2020.01221

Abstract

Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. It has important immunological properties, and is both antibacterial and antiviral. In particular, there is evidence that it can bind to at least some of the receptors used by coronaviruses and thereby block their entry. Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells. Lactoferrin (and more specifically enteric-coated LF because of increased bioavailability) may consequently be of preventive and therapeutic value during the present COVID-19 pandemic.

Highlights

Lactoferrin (LF) or lactotransferrin has recently come under the spotlight, with regards to the new coronavirus pandemic that started in 2019 (COVID-19)
We discuss how LF uses Heparan Sulfate Proteoglycans (HSPGs) on cell surfaces to facilitate entry. This is of particular importance to coronaviruses, as these viruses are considered to bind to the host cell by attaching first to Heparan sulfate proteoglycans (HSPG) using them as preliminary docking sites on the host cell surface
The binding of LF to HSPGs prevents the first contact between virus and host cells and prevents subsequent infection [99]

Summary

INTRODUCTION

Lactoferrin (LF) or lactotransferrin has recently come under the spotlight, with regards to the new coronavirus pandemic that started in 2019 (COVID-19). In COVID-19 infection, LF may have a role to play, sequestering iron and inflammatory molecules that are severely increased during the cytokine burst, and possibly in assisting by occupying receptors and HSPGs. LF might prevent virus accumulation by the host cell, as well as rolling activity and entering of the virus via the host receptor angiotensin-converting enzyme 2 (ACE2). The entry of bacteria, bacterial products or viruses into host cells may occur via some of these receptors Such binding evokes signaling systems and pathways involving, amongst others, mitogen-activated protein kinase (MAPK) [105], NF-κB [106], activator protein 1 (AP-1) [107], and various interferon regulatory factors (IRFs) [for a comprehensive review see [108]]. This binding capacity allows LF to compete with such molecules for receptor occupancy [113, 114], and plays

CONCLUSIONS

Findings

DATA AVAILABILITY STATEMENT