Virucidal Activity of Human Α- and Β-defensins against Hepatitis C Virus Genotype 4

Hepatitis C virus (HCV) is the major etiological agent of human non-A and non-B hepatitis affecting about 180 million people worldwide. The goal of the current study was to find effective anti-HCV proteins. As a result, defensins were selected as promising candidates due to their well-known anti-viral potential and small size. We conducted in vitro evaluation of two kinds of defensins (human α- and β-defensins and synthetic linear avian α-defensins) using tissue culture combined with reverse transcription nested PCR (RT-nested-PCR) and real-time PCR. Human α- and β-defensins showed strong anti-HCV activity in experiments on cellular protection, neutralization, and treatment at all concentrations used (10, 20 and 50 μg). The synthetic linear defensins could reach similar anti-HCV potential only at a noticeably higher concentration (250 μg) and do not show noticeable activity at 10 and 20 μg. This study suggests that defensins are potent anti-HCV agents

Structural Heterogeneity and Multifunctionality of Lactoferrin

Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities. This multifunctionality is determined by the fact that lactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions. Structurally, lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes. These lobes are unevenly glycosylated (with the C-lobe typically containing more N-linked glycosylation sites). Each lobe can bind a single ferric ion concomitantly with one bicarbonate anion. Lactoferrin and its lobes have a wide spectrum of antimicrobial and antiviral activities, with the antimicrobial and antiviral potentials dependent on the type of microbes and viruses. Often, the N-lobe possesses the majority of antimicrobial activities. In addition, lactoferrin and its lobes possess clear anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities

Structural Heterogeneity and Multifunctionality of Lactoferrin

Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities. This multifunctionality is determined by the fact that lactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions. Structurally, lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes. These lobes are unevenly glycosylated (with the C-lobe typically containing more N-linked glycosylation sites). Each lobe can bind a single ferric ion concomitantly with one bicarbonate anion. Lactoferrin and its lobes have a wide spectrum of antimicrobial and antiviral activities, with the antimicrobial and antiviral potentials dependent on the type of microbes and viruses. Often, the N-lobe possesses the majority of antimicrobial activities. In addition, lactoferrin and its lobes possess clear anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities

Natural Resources to Control COVID-19: Could Lactoferrin Amend SARS-CoV-2 Infectivity?

The world population is still facing the second wave of the COVID-19 pandemic. Such a challenge requires complicated tools to control, namely vaccines, effective cures, and complementary agents. Here we present one candidate for the role of an effective cure and/or complementary agent: lactoferrin. It is the cross-talking mediator between many organs/cellular systems in the body. It serves as a physiological, immunological, and anti-microbial barrier, and acts as a regulator molecule. Furthermore, lactoferrin has receptors on most tissues cells, and is a rich source for bioactive peptides, particularly in the digestive system. In the past months, in vitro and in vivo evidence has accumulated regarding lactoferrin’s ability to control SARS-CoV-2 infectivity in different indicated scenarios. Also, lactoferrin or whey milk (of human or other mammal’s origin) is a cheap, easily available, and safe agent, the use of which can produce promising results. Pharmaceutical and/or food supplementary formulas of lactoferrin could be particularly effective in controlling the gastrointestinal COVID-19-associated symptoms and could limit the fecal-oral viral infection transmission, through mechanisms that mimic that of norovirus infection control by lactoferrin via induction of intestinal innate immunity. This natural avenue may be effective not only in symptomatic patients, but could also be more helpful in asymptomatic patients as a main or adjuvant treatment

Disorder in Milk Proteins: Lactadherin Multifunctionality and Structure

Milk fat globule membrane (MFGM) is one of the milk components that is produced by the lactating mammary glands and released to the milk in the form of vesicles. MFGM surrounds milk fat globule secreted by the milk producing cells and has a complex structure containing various lipids (e.g., triacylglycerides, phospholipids, and cholesterol), proteins and other macromolecules. Among the proteinaceous components of MFGM is lactadherin, also known as milk fat globule-EGF factor 8 protein (MFG-E8). Being one of the main proteins present in MFGM, lactadherin is related to milk secretion, has antimicrobial and antiviral effects, and plays important roles in the immune defense as one of the immune system molecules. Furthermore, lactadherin belongs to the family of secreted extracellular matrix proteins, and clearly can be considered as a multifunctional (or moonlighting) glycoprotein involved in regulation of many biological and physiological processes, such as angiogenesis, atherosclerosis, haemostasis, phagocytosis, and tissue remodeling. This review focuses on the similarities and differences of lactadherin among different species and describes the main functions of this protein, as well as its structure

Antimicrobial Potentials and Structural Disorder of Human and Animal Defensins

Defensins are moonlighting peptides which are broadly distributed throughout all the living kingdoms. They play a multitude of important roles in human health and disease, possessing several immunoregulatory functions and manifesting broad antimicrobial activities against viruses, bacteria, and fungi. Based on their patterns of intramolecular disulfide bridges, these small cysteine-rich cationic proteins are divided into three major types, α-, β-, and θ-defensins, with the α- and β-defensins being further subdivided into a number of subtypes. The various roles played by the defensins in the innate (especially mucosal) and adoptive immunities place these polypeptides at the frontiers of the defense against the microbial invasions. Current work analyzes the antimicrobial activities of human and animal defensins in light of their intrinsic disorder propensities

In Vitro Exploration of the Anti-hcv Potential of the Synthetic Spacer Peptides Derived from Human, Bovine, and Camel Lactoferrins

Background: Chronic liver disease is often associated with the infection by hepatitis C virus (HCV), which is an enveloped RNA virus belonging to the Flaviviridae family. Many studies found that milk proteins, such as lactoferrin, might have profound antiviral activity against HCV. Various secretory fluids ranging from milk, to tears, saliva, and nasal secretion, and to bile and pancreatic juice, as well as neutrophils, mucosal surfaces, and blood contain a widely spread multifunctional glycoprotein, lactoferrin (Lf), structure of which can be depicted as two homologous domains connected by the short spacer peptide.Objective: This study aimed to understand the effectiveness of the synthetic peptides cLfsp, bLfsp, hLfsp1, and hLfsp2 corresponding to the spacer peptides of camel, bovine, and human Lfs, respectively, against HCV in in vitro settings. Method: We used RT-nested PCR to evaluate the antiviral activity of the synthesized spacer peptides against HCV infectivity in PBMC and HepG2 cells looking at their neutralization, protection, and intracellular treatment potentials. Results and Conclusion: We show that direct interaction of hLfsp1, hLfsp2, and bLfsp with viral particles is able to neutralize the HCV entry into HepG2 cells (with hLfsp2 being more potent neutralizer than hLfsp1 and bLfsp), whereas cLfsp does not show any neutralizing potential. Therefore, our analysis revealed that different spacer peptides are characterized by different antiviral potentials and use different mechanisms for antiviral protection

Challenges and obstacles faced by trainee female physicians: An integrative research on gender discrimination, stress, depression and harassment

This study’s purpose is to assess the challenges and obstacles faced by female trainee physicians and suggest solutions that could resolve these issues and improve their performance. The study utilized an observational, analytical, cross-sectional design based on a self-administered open-ended and validated questionnaire which was distributed to 133 recruited female resident trainees of medical units in Jeddah, Saudi Arabia. The findings of the study revealed that 52% female trainees experienced gender discrimination, mostly (65%) by their superiors, while 40% were regularly harassed. About half (53%) of the interviewees were severely depressed, resulting in their reconsidering their career in medicine. A total of 14% thought of suicide, while four planned to end and five had attempted to end their life. However, only eight (6%) participants officially reported the cases of harassment to the accountable superiors. Half of them felt neglected by the healthcare administration, and one-fourth (24%) were underachieving in their studies and work. The study concluded that work dissatisfaction, limited clinical correspondence, high depression, burnout, stress and drop-out rates—all deriving from common gender discrimination—compose the alarming and complex challenges that female trainee residents in Jeddah of various levels and specialties have to face. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Elevated Concentration of Defensins in Hepatitis C Virus-Infected Patients

Hepatitis C virus (HCV) is the major etiological agent of human non-A and non-B hepatitis, affecting around 180 million people worldwide. Defensins, small cysteine-rich cationic peptides, are shown to have potent antibacterial, antiviral, and antifungal properties. Defensins can be found in both normal and microbial infected patients, at variable concentrations. Notably, viral infections are often associated with elevated concentrations of defensins. The current study aimed to estimate the concentrations of total, α-, and β-defensins in serum taken from normal and HCV-infected patients. 12 healthy (noninfected) and 34 HCV-infected patients were enrolled. Standardized immunoassay kits were used to obtain serum concentrations of defensins. The obtained results were calibrated against kit standard reagents. Total defensin concentrations in HCV-infected patients were significantly higher (2- to 105-fold) compared to healthy individuals. The concentrations of α-defensins were also significantly elevated in the HCV-infected patients (31–1398 ng/50 μL). However, concentrations of β-defensins ranged from 44.5 ng/50 μL to 1056 ng/50 μL. The results did not reveal differences in serum defensin concentration between male and female HCV-infected patients. A-defensin concentration of ≥250 ng/50 μL was found to contain more β-defensins than total defensins and α-defensins. This study concludes, for the first time, that serum defensin levels are elevated in HCV-infected patients