Sialic acids are a group of nine-carbon α-keto acids. Sialic acid exists in more than 50 forms, with the natural types discovered as N-acetylneuraminic acid (Neu5Ac), deaminoneuraminic acid (2-keto-3-deoxy-nonulononic acid or Kdn), and N-glycolylneuraminic acid (Neu5Gc). Sialic acid level varies depending on the source, where edible bird\'s nest (EBN), predominantly Neu5Ac, is among the major sources of sialic acid. Due to its high nutritive value and complexity, sialic acid has been studied extensively through acid, aqueous, and enzymatic extraction. Although detection by chromatographic methods or mass spectrometry is common, the isolation and recovery work remained limited. Sialic acid is well-recognised for its bioactivities, including brain and cognition development, immune-enhancing, anti-hypertensive, anticancer, and skin whitening properties. Therefore, sialic acid can be used as a functional ingredient in the various industries. This paper reviews the current trend in the biochemistry, sources, extraction, and functions of sialic acids with special reference to EBN.

Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.

Sialic acids (SA) determine the degree of molecular hydrophilia, relieve binding together and their transportation, they increase mucin viscosity, stabilize the protein and membrane structure. Apart from that, SA are structural components of gangliosides participating in the formation of the outer layer of the plasma membrane. The degree of silyliation of glycoproteins and glycolipids is an important factor of molecular recognition in the cell, between the cells, between a cell and territorial matrix, as well as between a cell and some outer pathogenic factors. They can either mask the sites of recognition or be determinants of recognition. The most well-studied enzymes taking part in the SA metabolism and sialo-containing compounds are N-acetylneuraminate, cythydiltransferase, sialyltransferase, sialydase, aldolase SA and sialyl-O-acetylesterase. Numerous investigations have shown that aberrant sialylation is a specific feature of various changes and disorders of metabolism. Besides that, sialic acids are the first point of contact for different pathogenic microorganisms and the host\'s body due to their presence on the external surface of the cells and tissue of the mucous membrane. That is why the study of the above-mentioned various sialic acids fractions as well as of the activity of the enzymes participating in their metabolism in the blood plasma and tissues, and of the influence on the activity of these enzymes with the help of medicine can make an essential contribution to the diagnosis and treatment of many diseases.

Introduction: Despite the current interest caused by SARS-Cov-2, influenza continues to be one of the most serious health concerns, with an estimated 1 billion cases across the globe, including 3-5 million severe cases and 290,000-650,000 deaths worldwide. Areas covered: This manuscript reviews the efforts made in the development of small molecules for the treatment of influenza virus, primarily focused on patent applications in the last 5 years. Attention is paid to compounds targeting key functional viral proteins, such as the M2 channel, neuraminidase, and hemagglutinin, highlighting the evolution toward new ligands and scaffolds motivated by the emergence of resistant strains. Finally, the discovery of compounds against novel viral targets, such as the RNA-dependent RNA polymerase, is discussed. Expert opinion: The therapeutic potential of antiviral agents is limited by the increasing presence of resistant strains. This should encourage research on novel strategies for therapeutic intervention. In this context, the discovery of arbidol and JNJ7918 against hemagglutinin, and current efforts on RNA-dependent RNA polymerase have disclosed novel opportunities for therapeutic treatment. Studies should attempt to expand the therapeutic arsenal of anti-flu agents, often in combined therapies, to prevent future health challenges caused by influenza virus. Abbreviations: AlphaLISA: amplified luminescent proximity homogeneous assay; HA: hemagglutinin; NA: neuraminidase; RBD: receptor binding domain; RdRp: RNA-dependent RNA polymerase; SA: sialic Acid; TBHQ: tert-butyl hydroquinone; TEVC: two-electrode voltage clamp.

Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza.
The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009-2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events.
Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance.
Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit.

Sialidases are enzymes essential for numerous organisms including humans. Hydrolytic sialidases (EC 3.2.1.18), trans-sialidases and anhydrosialidases (intramolecular trans-sialidases, EC 4.2.2.15) are glycoside hydrolase enzymes that cleave the glycosidic linkage and release sialic acid residues from sialyl substrates. The paper summarizes diverse sialidases present in the human body and their potential impact on development of antiviral compounds - inhibitors of viral neuraminidases. It includes a brief overview of catalytic mechanisms of action of sialidases and describes the origin of sialidases in the human body. This is followed by description of the structure and function of sialidase families with a special focus on the GH33 and GH34 families. Various effects of sialidases on human body are also briefly described. Modulation of sialidase activity may be considered a useful tool for effective treatment of various diseases. In some cases, it is desired to completely suppress the activity of sialidases by suitable inhibitors. Specific sialidase inhibitors are useful for the treatment of influenza, epilepsy, Alzheimer\'s disease, diabetes, different types of cancer, or heart defects. Challenges and future directions are shortly depicted in the final part of the paper.

This report summarizes the discussions and conclusions from the \"Immunological Assays and Correlates of Protection for Next-Generation Influenza Vaccines\" meeting which took place in Siena, Italy, from March 31, 2019, to April 2, 2019.
Furthermore, we review current correlates of protection against influenza virus infection and disease and their usefulness for the development of next generation broadly protective and universal influenza virus vaccines.

Influenza is a long-standing health problem. For treatment of seasonal flu and possible pandemic infections, there is a need to develop new anti-influenza drugs that have good bioavailability against a broad spectrum of influenza viruses, including the resistant strains. Relenza™ (zanamivir), Tamiflu™ (the phosphate salt of oseltamivir), Inavir™ (laninamivir octanoate) and Rapivab™ (peramivir) are four anti-influenza drugs targeting the viral neuraminidases (NAs). However, some problems of these drugs should be resolved, such as oral availability, drug resistance and the induced cytokine storm. Two possible strategies have been applied to tackle these problems by devising congeners and conjugates. In this review, congeners are the related compounds having comparable chemical structures and biological functions, whereas conjugate refers to a compound having two bioactive entities joined by a covalent bond. The rational design of NA inhibitors is based on the mechanism of the enzymatic hydrolysis of the sialic acid (Neu5Ac)-terminated glycoprotein. To improve binding affinity and lipophilicity of the existing NA inhibitors, several methods are utilized, including conversion of carboxylic acid to ester prodrug, conversion of guanidine to acylguanidine, substitution of carboxylic acid with bioisostere, and modification of glycerol side chain. Alternatively, conjugating NA inhibitors with other therapeutic entity provides a synergistic anti-influenza activity; for example, to kill the existing viruses and suppress the cytokines caused by cross-species infection.

Recent advances in next-generation sequencing technologies have uncovered the genetic backgrounds of various diseases. Type 1 sialidosis (OMIM#256550) is a rare autosomal recessive lysosomal storage disease caused by a mutation in the NEU1 (OMIM * 608272) gene. In this study, we aimed to review the previous reports of type 1 sialidosis and compare those with the first case of type 1 sialidosis in Korea. A 36-year-old woman presented with progressive ataxia, myoclonus, and seizure since the age of 12. Whole-exome sequencing revealed a pathogenic missense variant c.928G > A (p.D310N) and novel c.15_16del (p.P6Qfs*21) of the NEU1 gene as final causal candidate as compound heterozygotes. We reviewed the literature and selected the clinical reports of genetically confirmed type 1 sialidosis patients. A total of 45 patients in 17 reports were identified. Cherry-red spot, myoclonus, ataxia, and seizure were reported in 51.2%, 100.0%, 87.8%, and 73.7% of patients, respectively. Abnormalities of cognitive function, EEG, and brain MRI and visual symptoms were reported in 22.2%, 40.7%, 66.7%, and 70.2% of patients, respectively. Overall, our patient showed similar clinical features to previous type 1 sialidosis patients, but she did not complain of visual symptoms despite having cherry-red spots. We summarize the clinical features of type 1 sialidosis and report the first case of type 1 sialidosis with novel deletion variant in the NEU1 gene in the Korean population. Our study suggests the importance of ophthalmologic examinations in patients with myoclonus, ataxia, and seizure who do not complain of visual symptoms.

The rapidly changing influenza virus has remained a consistent threat to the well-being of a variety of species on the planet. Influenza virus\' high mutation rate has allowed the virus to rapidly and continuously evolve, as well as generate new strains that are resistant to the current commercially available antivirals. Thus, the increased resistance has compelled the scientific community to explore alternative compounds that have antiviral effects against influenza virus. In this paper, the authors systematically review numerous herbal extracts that were shown to have antiviral effects against the virus. Specifically, the herbal antiviral targets mainly include hemagglutinin, neuraminidase and matrix 2 proteins. In some instances, herbal extracts inhibited the replication of oseltamivir-resistant strains and certain pentacyclic triterpenes exhibited higher antiviral activity than oseltamivir. This paper also explores the possibility of targeting various host-cell signaling pathways that are utilized by the virus during its replication process. Infected cell pathways are hijacked by intracellular signaling cascades such as NF-kB signaling, PI3K/Akt pathway, MAPK pathway and PKC/PKR signaling cascades. Herbal antivirals have been shown to target these pathways by suppressing nuclear export of influenza vRNP and thus inhibiting the phosphorylation signaling cascade. In conclusion, copious amounts of herbal antivirals have been shown to inhibit influenza virus, however further studies are needed for these new compounds to be up to modern pharmacological standards.