Endo-β-N-acetylglucosaminidase EndoE from infant gut Enterococcus faecalis neutralizes SARS-CoV-2 by interacting with the viral spike protein DOI Creative Commons
Eva M. Moya-Gonzálvez,

Sergi López-Navarro,

Roberto Gozalbo‐Rovira

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is extensively N-glycosylated, and unlike the receptor-binding domain of S1 subunit which undergoes frequent mutations, glycosylation sites remain conserved across most variants concern. In this study, we cloned purified EndoE, an endo-β-N-acetylglucosaminidase enzyme from Enterococcus faecalis strain isolated in our laboratory (E8 strain). The EndoE effectively removed glycans protein SARS-CoV-2 spike. We constructed a catalytically inactive mutant form termed (Mut). Both wild-type (Mut) demonstrated neutralizing activity against S pseudotyped virus infection, with IC50 values 81.26 ± 8.42 nM 63.15 5.06 nM, respectively. Enzyme-linked immunosorbent assay revealed that both forms bound to protein. Moreover, commercial EndoH enzyme, also cleaves N-glycosylation, did not exhibit at any tested concentration. contrast, plant lectin Concanavalin A potent neutralization ability, 40.89 24.04 nM. Importantly, neither displayed toxicity even highest concentration (6,250 nM), whereas exhibited cells as low 157 These findings shed light on role glycosidases infection offer novel avenue for development antiviral strategies.

Language: Английский

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications DOI Creative Commons
Somchai Chutipongtanate, Ardythe L. Morrow, David S. Newburg

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2345 - 2345

Published: July 30, 2022

The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk diarrheal disease, respiratory otitis media, and in later life, less chronic disease. These benefits may be mediated antibodies, glycoproteins, glycolipids, oligosaccharides, leukocytes. More recently, extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs proteins, that transmit information from the mother to promote growth development. Maternal conditions can influence hMEV composition. This review summarizes biogenesis contents, reviews evidence hMEVs maternal–infant relationship, discusses challenges opportunities research.

Language: Английский

Citations

46
Chemical synthesis of oligosaccharides and their application in new drug research DOI Creative Commons
Zhimin Lv, Hongyu Liu, Huifang Hao

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 249, P. 115164 - 115164

Published: Feb. 1, 2023

Language: Английский

Citations

25
Recent progress on health effects and biosynthesis of two key sialylated human milk oligosaccharides, 3′-sialyllactose and 6′-sialyllactose DOI
Yingying Zhu, Jiameng Zhang, Wenli Zhang

et al.

Biotechnology Advances, Journal Year: 2022, Volume and Issue: 62, P. 108058 - 108058

Published: Nov. 11, 2022

Language: Английский

Citations

37
Human Milk Oligosaccharides and Respiratory Syncytial Virus Infection in Infants DOI Creative Commons
Karina Merini Tonon, Somchai Chutipongtanate, Ardythe L. Morrow

et al.

Advances in Nutrition, Journal Year: 2024, Volume and Issue: 15(6), P. 100218 - 100218

Published: April 5, 2024

In infants worldwide, respiratory syncytial virus (RSV) is the leading cause of lower infections, including bronchiolitis, which a major source infant mortality. Bronchiolitis most common infection and hospitalization in first 6 mo life. Infant responses to RSV are highly diverse, with symptoms varying from asymptomatic or mild so severe as require mechanical ventilation. Breastfed present incidence less forms infections. Among multitude human milk bioactive compounds, oligosaccharides (hMOSs) strong candidates for having protective effect against RSV. hMOS reduces viral load inflammatory signaling cultured RSV-infected cells. addition this direct effect, indirect mechanisms, notably gut microbiota composition metabolism, have been proposed mediate hMOS. Intake formula containing synthetic has shown increase Bifidobacterium abundance that its metabolites, especially acetate, feces reduce tract infections during year Breastfeeding use promising approaches protect treat disease. Here, we review current evidence on role regard disease, attending knowledge gaps future research directions.

Language: Английский

Citations

8
Role of milk glycome in prevention, treatment, and recovery of COVID-19 DOI Creative Commons
Merve Kaplan, Arif Sercan Şahutoğlu, Sümeyye Sarıtaş

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 8, 2022

Milk contains all essential macro and micro-nutrients for the development of newborn. Its high therapeutic antimicrobial content provides an important function prevention, treatment, recovery certain diseases throughout life. The bioactive components found in milk are mostly decorated with glycans, which provide proper formation modulate biological functions glycosylated compounds. glycome consists free glycolipids, N- O- proteins. Recent studies have shown that both glycans glycan-containing molecules antiviral characteristics based on different mechanisms such as signaling, microbiome modulation, natural decoy strategy, immunomodulatory action. In this review, we discuss recent clinical potential conjugated glycans' role COVID-19.

Language: Английский

Citations

23
Human Milk Oligosaccharides: A Critical Review on Structure, Preparation, Their Potential as a Food Bioactive Component, and Future Perspectives DOI

Liuying Zhu,

Hongyan Li, Ting Luo

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(43), P. 15908 - 15925

Published: Oct. 18, 2023

Human milk is the gold standard for infant feeding. oligosaccharides (HMOs) are a unique group of in human milk. Great interest HMOs has grown recent years due to their positive effects on various aspects health. provide physiologic functions, including establishing balanced infant's gut microbiota, strengthening gastrointestinal barrier, preventing infections, and potential support immune system. However, clinical application challenging specificity difficulties high costs associated with isolation synthesis. Here, differences other mammalian compared, synthetic strategies access summarized. Additionally, use molecular mechanisms as new food bioactive component different diseases, such infection, necrotizing enterocolitis, diabetes, allergy, critically reviewed. Finally, current challenges prospects basic research discussed.

Language: Английский

Citations

16
Targeting host-virus interactions: in silico analysis of the binding of human milk oligosaccharides to viral proteins involved in respiratory infections DOI Creative Commons
Anees Ahmed Mahaboob Ali, Adarsh Vishal, Everette Jacob Remington Nelson

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 19, 2024

Abstract Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face emerging and re-emerging pathogens. In this study, we explored potential human milk oligosaccharides (HMOs) as broad-spectrum agents against key respiratory viruses. By examining structural mimicry host cell receptors their known biological functions, including activities, assessed ability HMOs to bind potentially inhibit proteins crucial for entry. Our silico analysis focused on integral host-virus interactions, namely hemagglutinin protein influenza, fusion syncytial metapneumovirus, spike SARS-CoV-2. Using molecular docking simulation studies, demonstrated that exhibit varying binding affinities these proteins, suggesting entry inhibitors. This study identified several with promising profiles, highlighting drug development. research provides foundation utilizing natural source designing new therapeutics, offering approach fight infections.

Language: Английский

Citations

5
Current Advances in Structure–Function Relationships and Dose-Dependent Effects of Human Milk Oligosaccharides DOI
Jin Wang,

Mengshan Chen,

Ruishan Wang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(21), P. 6328 - 6353

Published: May 20, 2022

HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, play an role regulating neonatal intestinal immunity, resisting viral and bacterial infections, displaying anti-inflammatory characteristics, promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing structure-activity relationships dose-dependent effects is lacking. Hence, after introducing structures synthetic pathways this summarizes categorizes identified structure-function HMOs. Differential mechanisms different structural utilization by microorganisms summarized. This also emphasizes recent advances interactions between health benefits variance dosage effect based on vitro cell tests, animal experiments, human intervention studies. The potential chemical structure, selection, physiological properties as functional foods vital for further understanding their future applications.

Language: Английский

Citations

22
In Vivo Evidence on the Emerging Potential of Non-Digestible Oligosaccharides as Therapeutic Agents in Bacterial and Viral Infections DOI Open Access

Amirmohammad Afsharnia,

Yang Cai, Arjen Nauta

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(6), P. 1068 - 1068

Published: March 19, 2025

The issue of antibiotic-resistant bacterial infections, coupled with the rise in viral pandemics and slow development new antibacterial antiviral treatments, underscores critical need for novel strategies to mitigate spread drug-resistant pathogens, enhance efficacy existing therapies, accelerate discovery deployment innovative antimicrobial solutions. One promising approach address these challenges is dietary supplementation non-digestible oligosaccharides (NDOs). NDOs, including human milk (HMOs), play a vital role shaping sustaining healthy gut microbiota. Beyond stimulating growth activity beneficial bacteria, NDOs can also interact directly pathogenic bacteria viruses. Their properties arise from their unique interactions pathogens ability modulate host’s immune system. function as decoy receptors, inhibit pathogen growth, bind toxins, stimulate host response, exhibit anti-biofilm properties, barrier protection. However, notable gap exists comprehensive assessment vivo clinical data on this topic. This review aims provide an in-depth overview evidence related effects various HMOs, focus discussing possible mechanisms action.

Language: Английский

Citations

0
Identification and validation of programmed cell death related biomarkers for the treatment and prevention COVID-19 DOI Creative Commons
Jie Yang,

YaoXi Tan,

Xing Liu

et al.

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: April 29, 2025

Programmed cell death (PCD) plays a key role in the progression of coronavirus disease 2019 (COVID-19). However, PCD-relevant biomarkers have not been fully discovered. The aim this study was to explore for treatment and prevention COVID-19. Bioinformatic analyses were performed clinical relevant PCD genes with differential expression (DE) COVID-19 compared matched controls. PPI network used hub screening machine learning methods employed filtering feature genes. biomarker screened by Venn diagram. correlations between features immune microenvironment further explored. Biomarker validation samples real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). In total, 118 clinically associated expressed (DEGs) screened, which mainly related apoptosis pathways, among six (Cyclin B1 (CCNB1), cyclin-dependent kinase 1 (CDK1), interferon regulatory factor 4 (IRF4), lipoteichoic acid (LTA), matrix metallopeptidase 9 (MMP9) Oncostatin M (OSM)) identified. excellent or good diagnostic performance determined receiver operating characteristic (ROC) curve analysis. showed diverse indicators, such as age, sex Intensive Care Unit (ICU) admission. Total 14 types cells exerted infiltration Biomarkers correlated at varying levels. classified three clusters, significant associations information, sex, age ICU DEGs patients relative (CCNB1, CDK1, IRF4, LTA, MMP9 OSM) can be served

Language: Английский

Citations

0