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Updated: Oct 30, 2025
Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus
Published on: October 1, 2015
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences
Elena Campione1, Caterina Lanna1, Terenzio Cosio1
1Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy.
Insights
Lactoferrin (Lf) demonstrates antiviral properties against SARS-CoV-2 by directly binding to the virus and host cells. This glycoprotein may offer a supplementary role in managing COVID-19 patients.
Area of Science:
- Biochemistry
- Virology
- Immunology
Background:
- Lactoferrin (Lf) is a cationic glycoprotein found in human secretions and at sites of inflammation.
- Lf exhibits antimicrobial activity by chelating iron and interacting with microbial surface components.
- Lf possesses anti-inflammatory properties by inhibiting proinflammatory cytokine gene synthesis, including IL-6.
Purpose of the Study:
- To investigate the potential antiviral activity of lactoferrin against SARS-CoV-2.
- To explore the mechanisms underlying lactoferrin's antiviral effects on SARS-CoV-2.
- To assess the potential of lactoferrin as a supplementary treatment for COVID-19.
Main Methods:
- In vitro assays were conducted to evaluate lactoferrin's antiviral activity against SARS-CoV-2.
- In silico analysis was performed to study the interaction between lactoferrin and the SARS-CoV-2 spike protein.
- Antiviral activity was assessed across varying concentrations of lactoferrin, multiplicity of infection, and cell types (Vero E6/Caco-2).
Main Results:
- Lactoferrin exhibited direct antiviral activity against SARS-CoV-2 in vitro by attaching to viral and cellular components.
- The observed antiviral effect was dependent on lactoferrin concentration, multiplicity of infection, and cell type.
- In silico modeling supported direct binding between lactoferrin and the SARS-CoV-2 spike protein, suggesting inhibition of viral entry.
Conclusions:
- Lactoferrin demonstrates significant in vitro antiviral activity against SARS-CoV-2.
- The mechanism involves direct interaction with the virus and host cell surface components, potentially blocking viral entry.
- Lactoferrin may serve as a potential supplementary agent in the management of COVID-19.
Abstract:
Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.
