Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro

Andreu et al., Viruses, doi:10.3390/v15040972

Apr 2023

Source PDF All Studies Meta AnalysisMeta

In Vitro study showing more potent antiviral activity for SARS-CoV-2 and HCoV229E with liposomal lactoferrin compared with free lactoferrin. Authors note that liposomal encapsulation has been shown to increase permeability, bioavailability, and time release.

13 preclinical studies support the efficacy of lactoferrin for COVID-19:

2 In Silico studies Cutone, Miotto

10 In Vitro studies Alves, Andreu, Cutone, Kobayashi-Sakamoto, Mirabelli, Ostrov, Piacentini, Salaris, Yathindranath, Yazawa

1 In Vivo animal study Berkowitz

Important missing comments or errors? Let us know.

1. Alves et al., Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States, Pharmaceuticals, doi:10.3390/ph16101352.mdpi.com, doi.org.

2. Andreu et al., Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro, Viruses, doi:10.3390/v15040972.mdpi.com, doi.org.

3. Berkowitz et al., Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics, International Journal of Molecular Sciences, doi:10.3390/ijms242115718.mdpi.com, doi.org.

4. Cutone et al., Lactoferrin binding to Sars-CoV-2 Spike glycoprotein protects host from infection, inflammation and iron dysregulation., Research Square, doi:10.21203/rs.3.rs-1605740/v1.researchsquare.com, doi.org.

5. Kobayashi-Sakamoto et al., Bovine lactoferrin suppresses the cathepsin-dependent pathway of SARS-CoV-2 entry in vitro, International Dairy Journal, doi:10.1016/j.idairyj.2023.105805.sciencedirect.com, doi.org.

6. Miotto et al., Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin, Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2021.607443.frontiersin.org, doi.org.

7. Mirabelli et al., Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2105815118.pnas.org, doi.org.

8. Ostrov et al., Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells, Pathogens, doi:10.3390/pathogens10111514.mdpi.com, doi.org.

9. Piacentini et al., Lactoferrin Inhibition of the Complex Formation between ACE2 Receptor and SARS CoV-2 Recognition Binding Domain, International Journal of Molecular Sciences, doi:10.3390/ijms23105436.mdpi.com, doi.org.

10. Salaris et al., Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro, Nutrients, doi:10.3390/nu13020328.mdpi.com, doi.org.

11. Yathindranath et al., Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection, International Journal of Nanomedicine, doi:10.2147/IJN.S448005.dovepress.com, doi.org.

12. Yazawa et al., Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19, Research Square, doi:10.21203/rs.3.rs-2676422/v1.researchsquare.com, doi.org.

Andreu et al., 15 Apr 2023, Spain, peer-reviewed, 4 authors. Contact: sandreu@cbm.csic.es (corresponding author), ines.ripa@cbm.csic.es, raquel.bello-morales@uam.es, ja.lopez@uam.es.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Lactoferrin All

AI generated summary. Current AI models can provide useful summaries for non-experts, but may be inaccurate and have limited ability to analyze larger context such as the entire evidence base for lactoferrin.

Liposomal lactoferrin was more effective than free lactoferrin at inhibiting HCoV-229E and SARS-CoV-2 pseudoviruses.

This article discusses the potential use of liposomal lactoferrin (Lf) as an antiviral treatment for COVID-19. Lf is a protein that is naturally found in human milk, saliva, and tears. It has a variety of beneficial properties, including anti-inflammatory, antioxidant, and immune-modulating effects. In vitro studies have shown that Lf can inhibit the growth of a variety of viruses, including SARS-CoV-2.

In the present study, the authors investigated the antiviral activity of liposomal Lf against HCoV-229E and SARS-CoV-2 pseudoviruses. They found that liposomal Lf was more effective than free Lf at inhibiting the growth of both viruses.

The authors conclude that liposomal Lf is a promising candidate for the development of an antiviral treatment for COVID-19. Further studies are needed to determine the efficacy and safety of liposomal Lf in humans.

Here are some additional details from the article:

Lf is a multifunctional protein that has been shown to have antiviral, anti-inflammatory, and immunomodulatory effects.
In vitro studies have shown that Lf can inhibit the growth of a variety of viruses, including SARS-CoV-2.
The authors of the present study found that liposomal Lf was more effective than free Lf at inhibiting the growth of HCoV-229E and SARS-CoV-2 pseudoviruses.
The authors conclude that liposomal Lf is a promising candidate for the development of an antiviral treatment for COVID-19.

Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro

Sabina Andreu, Inés Ripa, Raquel Bello-Morales, José Antonio López-Guerrero

Viruses, doi:10.3390/v15040972

A limited number of effective therapies are currently available to treat human coronavirus SARS-CoV-2 and other human coronaviruses, which are responsible for nearly a third of global cases of the common cold. The possibility of new emerging coronaviruses demands powerful new antiviral strategies. Lactoferrin is a well-known protein that possesses anti-inflammatory and immunomodulatory activities, and it has previously shown antiviral activity against several viruses, including SARS-CoV-2. To increase this antiviral activity, here we present bovine liposomal lactoferrin. Liposomal encapsulation of the compound was proven to increase permeability, bioavailability, and time release. In the present work, we compare the antiviral activity of free and liposomal bovine lactoferrin against HCoV229E and SARS-CoV-2 in vitro and in human primary bronchial epithelial cells, and we demonstrated that the liposomal form exerts a more potent antiviral activity than its free form at non-cytotoxic doses.

Informed Consent Statement: Written informed consent was obtained from the patient(s) to publish this paper. Conflicts of Interest: The authors declare no conflict of interest.

References

Andreu, Ripa, Praena, López-Guerrero, Bello-Morales, The Valproic Acid Derivative Valpromide Inhibits Pseudorabies Virus Infection in Swine Epithelial and Mouse Neuroblastoma Cell Lines, Viruses, doi:10.3390/v13122522

Berlutti, Pantanella, Natalizi, Frioni, Paesano et al., Antiviral Properties of Lactoferrin-A Natural Immunity Molecule, Molecules, doi:10.3390/molecules16086992

Bolat, Eker, Kaplan, Duman, Arslan et al., Lactoferrin for COVID-19 Prevention, Treatment, and Recovery, Front. Nutr, doi:10.3389/fnut.2022.992733

Campione, Lanna, Cosio, Rosa, Conte et al., Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence, Int J. Environ. Res. Public Health, doi:10.3390/ijerph182010985

Cutone, Rosa, Bonaccorsi Di Patti, Iacovelli, Conte et al., Lactoferrin Binding to SARS-CoV-2 Spike Glycoprotein Blocks Pseudoviral Entry and Relieves Iron Protein Dysregulation in Several In Vitro Models, Pharmaceutics, doi:10.3390/pharmaceutics14102111

Einerhand, Van Loo-Bouwman, Weiss, Wang, Ba et al., Can Lactoferrin, a Natural Mammalian Milk Protein, Assist in the Battle against COVID-19?, Nutrients, doi:10.3390/nu14245274

Enjuanes, Zuñiga, Castaño-Rodriguez, Gutierrez-Alvarez, Canton et al., Molecular Basis of Coronavirus Virulence and Vaccine Development, Adv. Virus Res, doi:10.1016/BS.AIVIR.2016.08.003

Farid, El Shemy, Nafie, Hegazy, Abdelhiee, Anti-Inflammatory, Anti-Oxidant and Hepatoprotective Effects of Lactoferrin in Rats, Drug Chem. Toxicol, doi:10.1080/01480545.2019.1585868

Gorbalenya, Baker, Baric, De Groot, Drosten et al., The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-NCoV and Naming It SARS-CoV-2, Nat. Microbiol, doi:10.1038/S41564-020-0695-Z

Grau-Expósito, Perea, Suppi, Massana, Vergara et al., Evaluation of SARS-CoV-2 Entry, Inflammation and New Therapeutics in Human Lung Tissue Cells, PLoS Pathog, doi:10.1371/journal.ppat.1010171

He, Qin, Guan, Liu, Hong et al., Bovine Lactoferrin Inhibits SARS-CoV-2 and SARS-CoV-1 by Targeting the RdRp Complex and Alleviates Viral Infection in the Hamster Model, J. Med. Virol, doi:10.1002/jmv.28281

Hoffmann, Hofmann-Winkler, Smith, Krüger, Arora et al., Camostat Mesylate Inhibits SARS-CoV-2 Activation by TMPRSS2-Related Proteases and Its Metabolite GBPA Exerts Antiviral Activi, ity. EBioMedicine, doi:10.1016/j.ebiom.2021.103255

Horndler, Delgado, Abia, Balabanov, Martínez-Fleta et al., Flow Cytometry Multiplexed Method for the Detection of Neutralizing Human Antibodies to the Native SARS-CoV-2.2 Spike Prot.tein, EMBO Mol. Med, doi:10.15252/emmm.202013549

Hu, Meng, Zhang, Xiang, Wang, The in Vitro Antiviral Activity of Lactoferrin against Common Human Coronaviruses and SARS-CoV-2 Is Mediated by Targeting the Heparan Sulfate Co-Receptor, Emerg Microbes Infect, doi:10.1080/22221751.2021.1888660

Indrayanto, Putra, Suhud, Validation of In-Vitro Bioassay Methods: Application in Herbal Drug Research, Profiles Drug Subst. Excip. Relat. Methodol, doi:10.1016/BS.PODRM.2020.07.005

Ishikado, Imanaka, Takeuchi, Harada, Makino, Liposomalization of Lactoferrin Enhanced It's Anti-Inflammatory Effects via Oral Administration, Biol. Pharm. Bull, doi:10.1248/bpb.28.1717

Kopaeva, Alchinova, Cherepov, Demorzhi, Nesterenko et al., New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose, Antioxidants, doi:10.3390/antiox11091833

Lang, Yang, Deng, Liu, Yang et al., Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans, PLoS ONE, doi:10.1371/journal.pone.0023710

Legrand, Elass, Carpentier, Mazurier, Interactions of Lactoferrin with Cells Involved in Immune Function, Biochem. Cell Biol, doi:10.1139/o06-045

Liu, Chen, Zhang, A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives, Molecules, doi:10.3390/molecules27041372

Mann, Ndung'u, The Potential of Lactoferrin, Ovotransferrin and Lysozyme as Antiviral and Immune-Modulating Agents in COVID-19, Future Virol, doi:10.2217/fvl-2020-0170

Martorell, Llopis, Gonzalez, Ramón, Serrano et al., A Nutritional Supplement Containing Lactoferrin Stimulates the Immune System, Extends Lifespan, and Reduces Amyloid β Peptide Toxicity in Caenorhabditis Elegans, Food Sci. Nutr, doi:10.1002/fsn3.388

Menéndez, Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective, Molecules, doi:10.3390/molecules27030658

Mesel-Lemoine, Millet, Vidalain, Law, Vabret et al., A Human Coronavirus Responsible for the Common Cold Massively Kills Dendritic Cells but Not Monocytes, J. Virol, doi:10.1128/JVI.00269-12

Nakabayashi, Miyano, Sato, Yamane, Taketa, Growth of Human Hepatoma Cells Lines with Differentiated Functions in Chemically Defined Medium, Cancer Res

Reed, Muench, A Simple Method of Estimating Fifty per Cent Endpoints, Am. J. Epidemiol, doi:10.1093/oxfordjournals.aje.a118408

Salaris, Scarpa, Elli, Bertolini, Guglielmetti et al., Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro, Nutrients, doi:10.3390/nu13020328

Serrano, Almudéver, Serrano, Milara, Torrens et al., Phosphatidylcholine Liposomes as Carriers to Improve Topical Ascorbic Acid Treatment of Skin Disorders, Clin. Cosmet. Investig. Dermatol, doi:10.2147/CCID.S90781

Serrano, Kochergina, Albors, Diaz, Oroval et al., Liposomal Lactoferrin as Potential Preventative and Cure for COVID-19, Int. J. Res. Health Sci, doi:10.5530/ijrhs.8.1.3

Serrano, Mullor, Sanchez, Kochergina, Albors et al., Liposomal Lactoferrin Effect in Preventing SARS-CoV-2 Binding in HACAT Keratinocytes, Int. J. Res. Health Sci, doi:10.5530/ijrhs.8.2.1

Siqueiros-Cendón, Arévalo-Gallegos, Iglessias-Figueroa, García-Montoya, Salazar-Martínez et al., Immunomodulatory Effects of Lactoferrin, Acta Pharmacol. Sin, doi:10.1038/aps.2013.200

Sokolov, Isakova-Sivak, Grudinina, Mezhenskaya, Litasova et al., Ferristatin II Efficiently Inhibits SARS-CoV-2 Replication in Vero Cells, Viruses, doi:10.3390/v14020317

Sokolov, Isakova-Sivak, Mezhenskaya, Kostevich, Gorbunov et al., Molecular Mimicry of the Receptor-Binding Domain of the SARS-CoV-2

Trie, Guillen, Vaughan, Telfer, Brewer et al., Liposomes as Possible Carriers for Lactoferrin in the Local Treatment of Inflammatory Diseases, Exp. Biol. Med, doi:10.1177/153537020122600608

Trif, Roseanu, Brock, Brewer, Designing Lipid Nanostructures for Local Delivery of Biologically Active Macromolecules, J. Liposome Res, doi:10.1080/08982100701530027

Vert, The Non-Specific Antiviral Activity of Polysulfates to Fight SARS-CoV-2, Its Mutants and Viruses with Cationic Spikes, J. Biomater. Sci. Polym. Ed, doi:10.1080/09205063.2021.1925391

Wang, Timilsena, Blanch, Adhikari, Lactoferrin: Structure, Function, Denaturation and Digestion, Crit. Rev. Food Sci. Nutr, doi:10.1080/10408398.2017.1381583

Wang, Wang, Wang, Luo, Wan et al., Lactoferrin for the Treatment of COVID-19 (Review), Exp. Ther. Med, doi:10.3892/etm.2020.9402

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0