Lactoferrin: A Promising Therapeutic Molecule against Human Papillomavirus

Abstract

Lactoferrin is a multifunctional glycoprotein naturally found in mammalian secretions, predominantly in colostrum and milk. As a key component of dairy foods, lactoferrin enhances viral protection and boosts human health, owing to its fundamental properties including antiviral, anti-inflammatory, and immune-modulatory effects. Importantly, the antiviral effect of lactoferrin has been shown against a range of viruses causing serious infections and threatening human health. One of the viruses that lactoferrin exerts significant antiviral effects on is the human papillomavirus (HPV), which is the most prevalent transmitted infection affecting a myriad of people around the world. Lactoferrin has a high potential to inhibit HPV via different mechanisms, including direct binding to viral envelope proteins or their cell receptors, thereby hindering viral entry and immune stimulation by triggering the release of some immune-related molecules through the body, such as lymphocytes. Along with HPV, lactoferrin also can inhibit a range of viruses including coronaviruses and hepatitis viruses in the same manner. Here, we overview the current knowledge of lactoferrin and its effects on HPV and other viral infections.

Keywords: HPV; antiviral; dairy foods; human papillomavirus; lactoferrin; milk; natural compound.

Figure 1

Potential antiviral effects of lactoferrin (PDB 1BLF) on papillomavirus. Lactoferrin can inhibit viral infection in its early stages by suppressing viral entry and/or inhibiting viral replication in further stages. It can directly attach to viral glycans found on their membranes and inhibit their binding to cell surface receptors (1a). It can also inhibit viral entry by binding to HSPGs, which are found on the cell membrane or free in the ECM, that are responsible for the viral entry mechanism (1b). It can bind to its receptors on the cell membrane and trigger some interferons that can prevent viral replication (2a) [6,8,18] (Created with BioRender.com).

Figure 2

HPV entry through host cells. HPV (type 16) attaches to laminin, free heparan sulfates in the ECM, or membrane (1,2), and the virus changed conformationally via exposing additional amino acids of the L2 N terminus. Then, the virion binds to integrin, which promotes intracellular signaling and further conformational changes (3). Following this, endocytosis of HPV16 takes place through the cytosol (4,5), lysozyme (6), and ER (7) to reach the nucleus [79,80,81] (Created with BioRender.com).

Figure 3

HPV infection and development of cervical cancer. HPV enters the basal cells via micro-abrasions in the cervical layer (1). Through further infection, the viral genome is replicated and progeny virions are formed to initiate a new infection which has a high risk to progress lesions (2,3). Untreated lesions are associated with early gene disruption (E2) and upregulation (E6–E7), which stimulates oncogene expression and invasive cancer development (4) [77]. (Created with BioRender.com).