PMC:7271924 / 972-4316 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7271924","sourcedb":"PMC","sourceid":"7271924","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7271924","text":"Introduction\nLactoferrin (LF) or lactotransferrin has recently come under the spotlight, particularly with regards to the new coronavirus pandemic that started in 2019 (COVID-19). Diet and supplements support a well-functioning immune system, and favorably influence the body's ability to fight infection. Although LF is produced by the body itself, as a secretion by exocrine glands (such as maternal milk or tears) and secondary granules of human neutrophils (1), it can also be taken as a supplement, where it then acts as nutraceutical or functional food. Our particular focus is on its role as an oral supplement. Here we also collate some of the evidence that shows how LF may be an important nutrient to support host immunity, including as an antibacterial and antiviral agent, but particularly with the current COVID-19 pandemic in mind.\nWe summarize what is already known about LF, including its immunological properties, as well as its antibacterial and antiviral activities. We also 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 HSPGs using them as preliminary docking sites on the host cell surface. LF is known to interfere with some of the receptors used by coronaviruses, it may thus contribute usefully to the prevention and treatment of SARS CoV-2 infections. In COVID-19 infection, LF may therefore have a role to play, not only sequestering iron and inflammatory molecules that are severely increased during the cytokine burst, but also possibly in assisting by occupying receptors and HSPGs. LF might also 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). It has been 20 years since the discovery of ACE2, and since its discovery it has been found to be expressed in numerous tissues, including the lungs and the cardiovascular system (2). During 2020, there has been a renewed interest in this receptor, due to the interactions of novel coronaviruses and their interactions with ACE2 (3–5). South and co-workers in 2020 also investigated whether ACE2 blockade is a suitable option to attenuate COVID-19 (5). The use of recombinant human ACE2 (rhACE2) as ACE receptor competitor for binding has also been investigated (6, 7). There is also interest in the therapeutic targeting of HSPGs, and Hondermarck and co-workers suggested that is seems an easy way to inhibit SARS-Cov-2 infectivity (8). Here we also suggest that LF might be used as both a preventive and therapeutic supplement in the COVID-19 pandemic, by preventing interactions between the virus and both HSPGs and possibly ACE2. We summarize the layout of this paper in Figure 1.\nFigure 1 Overview of this review of lactoferrin (LF). We discuss (1) discovery and structure of LF; (2) LF membrane receptors and some of the bacteria, their products and viruses that might also bind to these receptors, (3) including how acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (causing COVID-19) may interact with host cells (see Figure 6 and Conclusion for a detailed discussion); (4) and how LF assists with host immunity. Diagram created with BioRender 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