The Potential of lactoferrin, Ovotransferrin and Lysozyme As Antiviral and immune-modulating Agents in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), caused by SARS coronavirus 2 (SARS-CoV-2), is spreading rapidly with no established effective treatments. While most cases are mild, others experience uncontrolled inflammatory responses with oxidative stress, dysregulation of iron and coagulation as features. Lactoferrin, ovotransferrin and lysozyme are abundant, safe antimicrobials that have wide antiviral as well as immunomodulatory properties. In particular, lactoferrin restores iron homeostasis and inhibits replication of SARS-CoV, which is closely related to SARS-CoV-2. Ovotransferrin has antiviral peptides and activities that are shared with lactoferrin. Both lactoferrin and lysozyme are ‘immune sensing’ as they may stimulate immune responses or resolve inflammation. Mechanisms by which these antimicrobials may treat or prevent COVID-19, as well as sources and forms of these, are reviewed.

Lay abstract

Severe coronavirus disease (COVID-19) is characterized by systemic inflammation, where unbound iron plays a significant role in tissue injury. There is no established effective treatment for COVID-19, and some treatment options being explored are unlikely to be widely available soon, especially in resource-limited settings. An abundant and safe antimicrobial that could act via oral ingestion to lower the risk of infection or prevent mild cases from progressing to severe disease would be ideal. Tear lactoferrin and lysozyme levels predict the risk of acquiring upper respiratory tract infections, and these antimicrobials are abundant in nature. Lactoferrin binds free iron and it has been shown to inhibit replication of the novel coronavirus. Ovotransferrin is closely related to lactoferrin and is more abundant (in hen egg white) – it shares iron-binding and antiviral properties of lactoferrin. Lactoferrin, ovotransferrin and lysozyme have several overlapping effects on microbes as well as the immune system, whereby they enhance or limit immune activation in a manner appropriate to the immune environment. Importantly, oral ingestion of these proteins in human and animal studies has shown safety as well as systemic effects, with the ability to limit immune pathology. Research into these products to prevent or treat severe COVID-19 disease is warranted.

Keywords:

• COVID-19
• glycerol
• lactoferrin
• lysozyme
• novel coronavirus
• ovotransferrin

Acknowledgments

E Allen is acknowledged for her valuable contribution in the form of discussions on this topic.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.