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1.
Nutrients ; 14(15)2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1969398

ABSTRACT

The association of hyperinflammation and hyperferritinemia with adverse outcomes in SARS-CoV-2-infected patients suggests an integral role for iron homeostasis in pathogenesis, a commonly described symptom of respiratory viral infections. This dysregulated iron homeostasis results in viral-induced lung injury, often lasting long after the acute viral infection; however, much remains to be understood mechanistically. Lactoferrin is a multipurpose glycoprotein with key immunomodulatory, antimicrobial, and antiviral functions, which can be found in various secreted fluids, but is most abundantly characterized in milk from all mammalian species. Lactoferrin is found at its highest concentrations in primate colostrum; however, the abundant availability of bovine-dairy-derived lactoferrin (bLf) has led to the use of bLf as a functional food. The recent research has demonstrated the potential value of bovine lactoferrin as a therapeutic adjuvant against SARS-CoV-2, and herein this research is reviewed and the potential mechanisms of therapeutic targeting are considered.


Subject(s)
COVID-19 , Pandemics , Animals , COVID-19/drug therapy , Homeostasis , Iron/metabolism , Lactoferrin/pharmacology , Lactoferrin/therapeutic use , Mammals/metabolism , SARS-CoV-2
2.
J Oral Biosci ; 64(1): 108-113, 2022 03.
Article in English | MEDLINE | ID: covidwho-1926686

ABSTRACT

OBJECTIVES: Understanding the role of certain salivary components, such as TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM, in airway defense during the ongoing SARS-CoV-2 pandemic is essential. The salivary immune barrier of patients with COVID-19 may play a role in their prognosis. The present study aims to evaluate the impact of SARS-CoV-2 on saliva composition. METHODS: A longitudinal study was carried out with male and female firefighters aged 24-48 years. The study sample (n = 34) was divided into 3 groups: asymptomatic volunteers with a negative polymerase chain reaction (PCR) test for SARS-CoV-2 (group 1, Control, n = 21); patients with symptoms of COVID-19 of less than 7 days' duration and a diagnosis of SARS-CoV-2 infection by PCR (group 2, COVID-19, n = 13); and recovered patients from group 2 who were free of COVID-19 symptoms for at least 2 months (group 3, post-COVID-19 recovery, n = 13). All groups underwent real-time PCR to detect the presence of SARS-CoV-2, as well as analysis of the salivary concentrations of TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM by the ELISA method. RESULTS: Lactoferrin concentrations were significantly decreased in the infected group (COVID-19) when compared to those not infected by SARS-CoV-2 (control) (p = 0.032). IgA concentrations were decreased in the COVID-19 and post-COVID-19 groups compared to the control group (p = 0.005 and p = 0.016, respectively). Comparison of the COVID-19 and post-COVID-19 groups also revealed an increase in IgM concentrations during acute SARS-CoV-2 infection (p = 0.010). CONCLUSION: SARS-CoV-2 alters the composition of the salivary immune barrier.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/diagnosis , Female , Humans , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Interleukin-10 , Interleukin-6 , Lactoferrin , Longitudinal Studies , Male , Middle Aged , Muramidase , Saliva , Tumor Necrosis Factors/metabolism , Young Adult
3.
Front Immunol ; 13: 878201, 2022.
Article in English | MEDLINE | ID: covidwho-1892654

ABSTRACT

Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer's disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.


Subject(s)
Alzheimer Disease , COVID-19 , Aged , Alzheimer Disease/complications , Animals , Anti-Inflammatory Agents , COVID-19/complications , COVID-19/drug therapy , Cattle , Humans , Lactoferrin/therapeutic use , SARS-CoV-2
4.
Int J Mol Sci ; 23(10)2022 May 13.
Article in English | MEDLINE | ID: covidwho-1855645

ABSTRACT

The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum "physiological" lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD-ACE2 binding, bringing about a measurable, up to 300-fold increase of the KD value relative to RBD-ACE2 complex formation.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Lactoferrin , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Humans , Lactoferrin/metabolism , Peptidyl-Dipeptidase A/metabolism , Protein Interaction Domains and Motifs , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
5.
Int J Environ Res Public Health ; 19(9)2022 04 26.
Article in English | MEDLINE | ID: covidwho-1809909

ABSTRACT

(1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages.


Subject(s)
COVID-19 , Pelargonium , Humans , Lactoferrin , Molecular Docking Simulation , Pelargonium/chemistry , Plant Extracts/chemistry , SARS-CoV-2
6.
J Dairy Sci ; 105(4): 2791-2802, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1699602

ABSTRACT

Bovine lactoferrin (bLF), a naturally occurring glycoprotein found in milk, has bioactive characteristics against many microbes, viruses, and other pathogens. Bovine lactoferrin strongly inhibits SARS-CoV-2 infection in vitro through direct entry inhibition and immunomodulatory mechanisms. This study reports on the anti-SARS-CoV-2 efficacy of commercially available bLF and common dairy ingredients in the human lung cell line H1437 using a custom high-content imaging and analysis pipeline. We also show for the first time that bLF has potent efficacy across different viral strains including the South African B.1.351, UK B.1.1.7, Brazilian P.1, and Indian Delta variants. Interestingly, we show that bLF is most potent against the B.1.1.7 variant [half-maximal inhibitory concentration (IC50) = 3.7 µg/mL], suggesting that this strain relies on entry mechanisms that are strongly inhibited by bLF. We also show that one of the major proteolysis products of bLF, lactoferricin B 17-41, has a modest anti-SARS-CoV-2 activity that could add to the clinical significance of this protein for SARS-CoV-2 treatment as lactoferricin is released by pepsin during digestion. Finally, we show that custom chewable lactoferrin tablets formulated in dextrose or sorbitol have equivalent potency to unformulated samples and provide an option for future human clinical trials. Lactoferrin's broad inhibition of SARS-CoV-2 variants in conjunction with the low cost and ease of production make this an exciting clinical candidate for treatment or prevention of SARS-CoV-2 in the future.


Subject(s)
COVID-19 , Lactoferrin , Animals , COVID-19/veterinary , Humans , Lactoferrin/pharmacology , Milk , SARS-CoV-2
7.
Nutrients ; 13(2)2021 Jan 23.
Article in English | MEDLINE | ID: covidwho-1575478

ABSTRACT

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Gene Expression Regulation , Immunity, Innate/drug effects , Lactoferrin/pharmacology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/pathology , COVID-19/prevention & control , Caco-2 Cells , Chlorocebus aethiops , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Humans , Vero Cells
8.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1480796

ABSTRACT

Lactoferrins are an iron-binding glycoprotein that have important protective roles in the mammalian body through their numerous functions, which include antimicrobial, antitumor, anti-inflammatory, immunomodulatory, and antioxidant activities. Among these, their antimicrobial activity has been the most studied, although the mechanism behind antimicrobial activities remains to be elucidated. Thirty years ago, the first lactoferrin-derived peptide was isolated and showed higher antimicrobial activity than the native lactoferrin lactoferricin. Since then, numerous studies have investigated the antimicrobial potencies of lactoferrins, lactoferricins, and other lactoferrin-derived peptides to better understand their antimicrobial activities at the molecular level. This review defines the current antibacterial, antiviral, antifungal, and antiparasitic activities of lactoferrins, lactoferricins, and lactoferrin-derived peptides. The primary focus is on their different mechanisms of activity against bacteria, viruses, fungi, and parasites. The role of their structure, amino-acid composition, conformation, charge, hydrophobicity, and other factors that affect their mechanisms of antimicrobial activity are also reviewed.


Subject(s)
Anti-Infective Agents/pharmacology , Lactoferrin/pharmacology , Peptides/pharmacology , Animals , Anti-Infective Agents/chemistry , Humans , Hydrophobic and Hydrophilic Interactions , Lactoferrin/chemistry , Molecular Structure , Structure-Activity Relationship
9.
Int J Environ Res Public Health ; 18(20)2021 10 19.
Article in English | MEDLINE | ID: covidwho-1477947

ABSTRACT

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.


Subject(s)
COVID-19 , Lactoferrin , Animals , Antiviral Agents/therapeutic use , Cattle , Humans , RNA, Viral , SARS-CoV-2
10.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Article in English | MEDLINE | ID: covidwho-1437673

ABSTRACT

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.


Subject(s)
COVID-19 , Colitis, Ulcerative , Disulfiram/pharmacokinetics , Lactoferrin , Systemic Inflammatory Response Syndrome , Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Biomimetic Materials/pharmacology , COVID-19/drug therapy , COVID-19/immunology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Disease Models, Animal , Disulfiram/pharmacology , Drug Carriers/pharmacology , Humans , Immunosuppressive Agents/pharmacology , Lactoferrin/metabolism , Lactoferrin/pharmacology , Lipopolysaccharides/immunology , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred C57BL , Nanoparticles/therapeutic use , Pyroptosis/drug effects , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/metabolism , Treatment Outcome
11.
Molecules ; 26(2)2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-1389464

ABSTRACT

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.


Subject(s)
Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Peptides/chemistry , Peptides/pharmacology , Peptides/therapeutic use , Amino Acids/chemistry , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Computer Simulation , Cosmeceuticals/chemistry , Cosmeceuticals/therapeutic use , Dietary Supplements , Gene Transfer Techniques , Humans , Lactoferrin/chemistry , Lipid Bilayers , Nanostructures/administration & dosage , Nanostructures/chemistry , Peptides/administration & dosage , Stem Cells , Vaccines, Subunit/chemistry , Vaccines, Subunit/pharmacology
12.
Clin Nutr ESPEN ; 45: 26-32, 2021 10.
Article in English | MEDLINE | ID: covidwho-1385307

ABSTRACT

BACKGROUND: Lactoferrin (Lf) is one of the key immunomodulatory substances found naturally in various body fluids, such as saliva, tears, and breast milk, and forms a vital part of the innate defense against invading pathogens. Various studies have demonstrated antibacterial, antifungal, and antiviral properties of Lf and its protective role against respiratory tract infections (RTIs). The present meta-analysis aims to elucidate the association of Lf administration in reducing the risk of RTIs by systematically reviewing the data from randomized controlled trials (RCTs). METHODS: We systematically searched PubMed, Cochrane Library, Medline & CINAHL, Turning Research into Practice (TRIP), ProQuest Theses & Dissertations Databases, and China National Knowledge Infrastructure (CNKI) from inception till March 15, 2021. The primary outcome measure was a reduction in respiratory illness; decrease in frequency, symptoms, and duration. Random-effects model was used to estimate the odds ratio (OR) and 95% confidence interval (CI). We used Cochrane's RoB-2 to appraise the risk of bias of included RCTs. RESULTS: A total of nine RCTs were eligible for this review, of which six were included in the meta-analysis. Overall, two studies demonstrated a high risk of bias. The meta-analysis revealed a significantly reduced odds of developing respiratory infections with the use of Lf relative to the control (pooled odds ratio = 0.57; 95% confidence interval 0.44 to 0.74, n = 1,194), with sufficient evidence against the hypothesis of 'no significant difference' at the current sample size. CONCLUSIONS: The administration of Lf shows promising efficacy in reducing the risk of RTIs. Current evidence also favours Lf fortification of infant formula. Lf may also have a beneficial role in managing symptoms and recovery of patients suffering from RTIs and may have potential for use as an adjunct in COVID-19, however this warrants further evidence from a large well-designed RCT.


Subject(s)
COVID-19 , Respiratory Tract Infections , Female , Humans , Lactoferrin , Randomized Controlled Trials as Topic , Respiratory Tract Infections/prevention & control , SARS-CoV-2
13.
Medicina (Kaunas) ; 57(8)2021 Aug 19.
Article in English | MEDLINE | ID: covidwho-1367868

ABSTRACT

Background and Objectives: Preventive, adjunctive and curative properties of lactoferrin have been evaluated since the first wave of severe acute respiratory syndrome coronavirus (SARS-CoV), a viral respiratory disease, emerged 18 years ago. Despite the discovery of new vaccine candidates, there is currently no widely approved treatment for SARS-CoV-2 (COVID-19). Strict adherence to infection prevention and control procedures, as well as vaccines, can, however, prevent the spread of SARS-CoV-2. This study aimed to evaluate the efficacy of lactoferrin treatment in improving clinical symptoms and laboratory indices among individuals with mild to moderate coronavirus disease-19 (COVID-19). Materials and Method: A randomized, prospective, interventional pilot study conducted between 8 July and 18 September 2020 used a hospital-based sample of 54 laboratory-confirmed participants with mild to moderate symptoms of COVID-19. Randomization into a control and two treatment groups ensured all groups received the approved Egyptian COVID-19 management protocol; only treatment group participants received lactoferrin at different doses for seven days. Clinical symptoms and laboratory indices were assessed on Days 0, 2 and 7 after starting treatments. Mean values with standard deviation and one-way analysis of variance with least significant difference of demographic and laboratory data between control and treatment groups were calculated. Results: Our study showed no statistically significant difference among studied groups regarding recovery of symptoms or laboratory improvement. Conclusions: Further research into therapeutic properties particularly related to dosage, duration and follow-up after treatment with lactoferrin in individuals with COVID-19 is required.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Lactoferrin/therapeutic use , Pilot Projects , Prospective Studies , Treatment Outcome
14.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Article in English | MEDLINE | ID: covidwho-1366851

ABSTRACT

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious agents against SARS-CoV-2. From a library of 1,425 US Food and Drug Administration (FDA)-approved compounds and clinical candidates, we identified 17 hits that inhibited SARS-CoV-2 infection and analyzed their antiviral activity across multiple cell lines, including lymph node carcinoma of the prostate (LNCaP) cells and a physiologically relevant model of alveolar epithelial type 2 cells (iAEC2s). Additionally, we found that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exacerbate SARS-CoV-2 infection in vitro. Notably, we discovered that lactoferrin, a glycoprotein found in secretory fluids including mammalian milk, inhibits SARS-CoV-2 infection in the nanomolar range in all cell models with multiple modes of action, including blockage of virus attachment to cellular heparan sulfate and enhancement of interferon responses. Given its safety profile, lactoferrin is a readily translatable therapeutic option for the management of COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Immunologic Factors/pharmacology , Lactoferrin/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Virus Replication/drug effects , Animals , COVID-19/drug therapy , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Caco-2 Cells , Cell Line, Tumor , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Discovery , Drug Repositioning/methods , Epithelial Cells , Heparitin Sulfate/antagonists & inhibitors , Heparitin Sulfate/immunology , Heparitin Sulfate/metabolism , Hepatocytes , High-Throughput Screening Assays , Humans , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Vero Cells
15.
Gut Microbes ; 13(1): 1961970, 2021.
Article in English | MEDLINE | ID: covidwho-1348030

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic of coronavirus disease 2019 (COVID-19), which primarily manifests with respiratory distress and may also lead to symptoms associated with the gastrointestinal tract. Probiotics are living microorganisms that have been shown to confer immune benefits. In this study, we investigated the immunomodulatory effects and anti-SARS-CoV-2 activity of three different Lacticaseibacillus probiotic strains, either alone or in combination with lactoferrin, using the intestinal epithelial Caco-2 cell line. Our results revealed that the Lacticaseibacillus paracasei DG strain significantly induced the expression of genes involved in protective antiviral immunity and prevented the expression of proinflammatory genes triggered by SARS-CoV-2 infection. Moreover, L. paracasei DG significantly inhibited SARS-CoV-2 infection in vitro. L. paracasei DG also positively affected the antiviral immune activity of lactoferrin and significantly augmented its anti-SARS-CoV-2 activity in Caco-2 intestinal epithelial cells. Overall, our work shows that the probiotic strain L. paracasei DG is a promising candidate that exhibits prophylactic potential against SARS-CoV-2 infection.


Subject(s)
COVID-19/prevention & control , Lactobacillus/physiology , Lactoferrin/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Caco-2 Cells , Humans , Pandemics/prevention & control
16.
Cells ; 10(7)2021 07 17.
Article in English | MEDLINE | ID: covidwho-1323129

ABSTRACT

Central nervous system (CNS) diseases are currently one of the major health issues around the world. Most CNS disorders are characterized by high oxidative stress levels and intense inflammatory responses in affected tissues. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein, plays a significant role in anti-inflammatory, antibacterial, antiviral, reactive oxygen species (ROS) modulator, antitumor immunity, and anti-apoptotic processes. Previous studies have shown that Lf is abnormally expressed in a variety of neurological diseases, especially neurodegenerative diseases. Recently, the promotion of neurodevelopment and neuroprotection by Lf has attracted widespread attention, and Lf could be exploited both as an active therapeutic agent and drug nanocarrier. However, our understanding of the roles of Lf proteins in the initiation or progression of CNS diseases is limited, especially the roles of Lf in regulating neurogenesis. This review highlights recent advances in the understanding of the major pharmacological effects of Lf in CNS diseases, including neurodegenerative diseases, cerebrovascular disease, developmental delays in children, and brain tumors.


Subject(s)
Central Nervous System Diseases/metabolism , Lactoferrin/metabolism , Animals , Brain/embryology , Brain/pathology , Child , Child Development , Humans , Neurodevelopmental Disorders/pathology
17.
Front Immunol ; 12: 582556, 2021.
Article in English | MEDLINE | ID: covidwho-1311372

ABSTRACT

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.


Subject(s)
COVID-19/complications , COVID-19/prevention & control , Dietary Supplements , SARS-CoV-2 , Berberine/therapeutic use , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Fatty Acids, Omega-3/therapeutic use , Fungal Polysaccharides/therapeutic use , Humans , Lactoferrin/therapeutic use , Minerals/therapeutic use , Plant Lectins/therapeutic use , Polyphenols/therapeutic use , Soy Foods , Vitamins/therapeutic use
18.
Ocul Immunol Inflamm ; 29(4): 751-752, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1307412

ABSTRACT

Coronavirus-19 (Covid-19), which has affected the whole world in a very short time, can infect the eye by using the Angiotensin-Converting Enzyme 2 receptor. Viral prevalence in the conjunctiva was reported to be between 3% and 16% in patients with Covid-19. Although Covid-19 has been reported to cause symptoms of conjunctivitis and rash in the eye, no complete evidence has yet been presented that the virus is transmitted from the eye. The low rate of PCR positivity in conjunctival swabs may be due to the effect of lactoferrin (LF), which is among the tear defense systems. LF, the natural protein found in tears, plays a major role in the eye's immune system. The antiviral effect of LF on the SARS-CoV pseudotype, which is in the same family as SARS-CoV-2, has been demonstrated in-vitro.


Subject(s)
COVID-19/complications , Eye Infections, Viral/prevention & control , Lactoferrin/therapeutic use , SARS-CoV-2 , Anti-Infective Agents/therapeutic use , COVID-19/virology , Eye Infections, Viral/etiology , Humans
19.
Eur Rev Med Pharmacol Sci ; 25(11): 4174-4184, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1281023

ABSTRACT

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Immunologic Factors/immunology , Immunologic Factors/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Humans , Immunologic Factors/pharmacology , Lactoferrin/immunology , Lactoferrin/pharmacology , Lactoferrin/therapeutic use , Tretinoin/immunology , Tretinoin/pharmacology , Tretinoin/therapeutic use
20.
Rev Med Virol ; 32(1): e2261, 2022 01.
Article in English | MEDLINE | ID: covidwho-1252047

ABSTRACT

It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.


Subject(s)
Anti-Infective Agents/administration & dosage , COVID-19/prevention & control , Lactoferrin/administration & dosage , Virus Diseases/prevention & control , Anti-Infective Agents/therapeutic use , Humans , Lactoferrin/therapeutic use , SARS-CoV-2 , Virus Diseases/drug therapy
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