lactoferrin and Coronavirus-Infections

Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.

Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Inflammation; Intestinal Mucosa; Iron; Lactoferrin; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Respiratory Mucosa; SARS-CoV-2; Virus Internalization

The coronavirus disease 2019 (COVID-19) pandemic is rapidly advancing across the globe despite drastic public and personal health measures. Antivirals and nutritional supplements have been proposed as potentially useful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19, but few have been clinically established. Lactoferrin (Lf) is a naturally occurring, non-toxic glycoprotein that is orally available as a nutritional supplement and has established in vitro antiviral efficacy against a wide range of viruses, including SARS-CoV, a closely related coronavirus to SARS-CoV-2. Furthermore, Lf possesses unique immunomodulatory and anti-inflammatory effects that may be especially relevant to the pathophysiology of severe COVID-19 cases. Here we review the underlying biological mechanisms of Lf as an antiviral and immune regulator, and propose its unique potential as a preventative and adjunct treatment for COVID-19. We hope that further research and development of Lf nutritional supplementation would establish its role for COVID-19.

Topics: Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Heparan Sulfate Proteoglycans; Humans; Immunologic Factors; Interferons; Lactoferrin; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Virus Internalization; Virus Replication

Lactoferrin is a naturally occurring iron-binding glycoprotein, produced and secreted by mucosal epithelial cells and neutrophils in various mammalian species, including humans. It is typically found in fluids like saliva, milk and tears, where it reaches the maximum concentration. Thanks to its unique anti-inflammatory, antioxidant and antimicrobial activities, topical application of lactoferrin plays a crucial role in the maintenance of a healthy ocular surface system. The present review aims to provide a comprehensive evaluation of the clinical applications of lactoferrin in ocular diseases. Besides the well-known antibacterial effect, novel interest has been rising towards its potential application in the field of dry eye and viral infections. A growing body of evidence supports the antimicrobial efficacy of lactoferrin, which is not limited to its iron-chelating properties but also depends on its capability to directly interact with pathogen particles while playing immunomodulatory effects. Nowadays, lactoferrin antiviral activity is of special interest, since lactoferrin-based eye drops could be adopted to treat/prevent the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which has conjunctivitis among its possible clinical manifestations. In the future, further data from randomized controlled studies are desirable to confirm the efficacy of lactoferrin in the wide range of ocular conditions where it can be used.

Topics: Animals; Anti-Infective Agents; Conjunctivitis; Coronavirus Infections; COVID-19; Dry Eye Syndromes; Humans; Lactoferrin; Pandemics; Pneumonia, Viral

Two conundrums puzzle COVID-19 investigators: 1) morbidity and mortality is rare among infants and young children and 2) rates of morbidity and mortality exhibit large variances across nations, locales, and even within cities. It is found that the higher the rate of pneumococcal vaccination in a nation (or city) the lower the COVID-19 morbidity and mortality. Vaccination rates with Bacillus Calmette-Guerin, poliovirus, and other vaccines do not correlate with COVID-19 risks, nor do COVID-19 case or death rates correlate with number of people in the population with diabetes, obesity, or adults over 65. Infant protection may be due to maternal antibodies and antiviral proteins in milk such as lactoferrin that are known to protect against coronavirus infections. Subsequent protection might then be conferred (and correlate with) rates of Haemophilus influenzae type B (Hib) (universal in infants) and pneumococcal vaccination, the latter varying widely by geography among infants, at-risk adults, and the elderly. Also see the video abstract here https://youtu.be/GODBYRbPL00.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Betacoronavirus; Child; Child, Preschool; Coronavirus Infections; COVID-19; Female; Geography; Haemophilus influenzae type b; Humans; Infant; Infant Mortality; Infant, Newborn; Lactoferrin; Male; Middle Aged; Mortality; Pandemics; Pneumococcal Vaccines; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Vaccination; Vaccination Coverage; Young Adult

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Infant Mortality; Lactoferrin; Pandemics; Pneumonia, Viral; SARS-CoV-2; Vaccination; Vaccines

To initiate infections, many coronaviruses use sialic acids, either as receptor determinants or as attachment factors helping the virus find its receptor underneath the heavily glycosylated mucus layer. In the present study, the role of sialic acids in serotype I feline enteric coronavirus (FECV) infections was studied in feline intestinal epithelial cell cultures. Treatment of cells with neuraminidase (NA) enhanced infection efficiency, showing that terminal sialic acid residues on the cell surface were not receptor determinants and even hampered efficient virus-receptor engagement. Knowing that NA treatment of coronaviruses can unmask viral sialic acid binding activity, replication of untreated and NA-treated viruses was compared, showing that NA treatment of the virus enhanced infectivity in untreated cells, but was detrimental in NA-treated cells. By using sialylated compounds as competitive inhibitors, it was demonstrated that sialyllactose (2,6-α-linked over 2,3-α-linked) notably reduced infectivity of NA-treated viruses, whereas bovine submaxillary mucin inhibited both treated and untreated viruses. In desialylated cells, however, viruses were less prone to competitive inhibition with sialylated compounds. In conclusion, this study demonstrated that FECV had a sialic acid binding capacity, which was partially masked by virus-associated sialic acids, and that attachment to sialylated compounds could facilitate enterocyte infections. However, sialic acid binding was not a prerequisite for the initiation of infection and virus-receptor engagement was even more efficient after desialylation of cells, indicating that FECV requires sialidases for efficient enterocyte infections.

Topics: Animals; Cat Diseases; Cats; Cell Line; Coronavirus Infections; Coronavirus, Feline; Epithelial Cells; Feline Infectious Peritonitis; Fetuins; Gastric Mucins; Intestinal Mucosa; Lactoferrin; Lactose; Neuraminidase; Receptors, Virus; Sialic Acids; Virus Attachment