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Lactoferrin is an iron-binding glycoprotein present in most human exocrine fluids, particularly breast milk. Lactoferrin is also released from neutrophil granules, and its concentration increases rapidly at the site of inflammation. Immune cells of both the innate and the adaptive immune system express receptors for lactoferrin to modulate their functions in response to it. On the basis of these interactions, lactoferrin plays many roles in host defense, ranging from augmenting or calming inflammatory pathways to direct killing of pathogens. Complex biological activities of lactoferrin are determined by its ability to sequester iron and by its highly basic N-terminus, via which lactoferrin binds to a plethora of negatively charged surfaces of microorganisms and viruses, as well as to mammalian cells, both normal and cancerous. Proteolytic cleavage of lactoferrin in the digestive tract generates smaller peptides, such as N-terminally derived lactoferricin. Lactoferricin shares some of the properties of lactoferrin, but also exhibits unique characteristics and functions. In this review, we discuss the structure, functions, and potential therapeutic uses of lactoferrin, lactoferricin, and other lactoferrin-derived bioactive peptides in treating various infections and inflammatory conditions. Furthermore, we summarize clinical trials examining the effect of lactoferrin supplementation in disease treatment, with a special focus on its potential use in treating COVID-19. [ABSTRACT FROM AUTHOR]

The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).