Antiviral Properties of Lactoferrin—A Natural Immunity Molecule Original paper

What was reviewed?

This review explored the broad-spectrum antiviral effects of lactoferrin (Lf), emphasizing its mechanistic actions across various viral families. The paper examined how both human and bovine lactoferrin, as well as derivative peptides like lactoferricin, inhibit the infection cycles of enveloped and non-enveloped viruses. It focused on Lf’s ability to block viral attachment, entry, and intracellular replication, and reviewed in vitro and in vivo findings spanning herpesviruses, HIV, hepatitis viruses, and respiratory pathogens.

Who was reviewed?

The authors synthesized studies involving a wide range of viruses, including Herpes Simplex Virus (HSV), HIV, Hepatitis B and C, Human Papillomavirus (HPV), Influenza A, Adenovirus, Cytomegalovirus (CMV), Rotavirus, Poliovirus, and Japanese Encephalitis Virus, among others. The review encompassed cellular studies using epithelial, fibroblast, and immune-derived cell lines, as well as several in vivo animal models (e.g., mice, rats, and transgenic species).

What were the most important findings?

Lactoferrin exerts antiviral activity primarily in the early stages of viral infection by binding either to host cell surface glycosaminoglycans (like heparan sulfate) or directly to viral envelope proteins, thereby blocking viral adhesion and entry. This mechanism is consistent across HSV, HIV, CMV, and several respiratory and enteric viruses. Additionally, Lf prevents virus-induced apoptosis and modulates inflammatory responses in infected tissues. The antiviral activity appears independent of iron saturation but is enhanced in some cases by zinc or manganese saturation.

From a microbiome context, these actions preserve epithelial barrier integrity and limit downstream inflammation, which is critical in preventing secondary dysbiosis. By preventing viral entry, especially in the mucosal interface, Lf supports immune homeostasis without inducing widespread microbial suppression. In viruses like HSV and HIV, lactoferrin also reduces syncytium formation and virus-mediated immune evasion, indirectly benefiting mucosal microbial stability.

What are the implications of this review?

Lactoferrin is positioned as a valuable adjunct in antiviral therapy, with utility in both prevention and early treatment. Its broad mechanism of action, including blocking host-virus interactions, reducing apoptosis, and regulating inflammation, offers therapeutic promise across multiple viral infections. This mucosal protection is particularly relevant for the microbiome, as viral damage to epithelial surfaces often precedes microbial imbalance. While human trials are still limited, the convergence of in vitro and in vivo findings supports lactoferrin’s future integration into antiviral, microbiome-stabilizing therapies, particularly in settings like viral gastroenteritis, respiratory infections, and sexually transmitted viral diseases.