Search Results (439)

Influenza viruses remain a major global public health concern, causing significant morbidity and mortality annually despite widespread vaccination efforts. The limitations of current seasonal vaccines, including strain-specific efficacy and manufacturing delays, have accelerated the development of next-generation candidates aiming for universal protection. This review comprehensively summarizes the recent progress in universal influenza vaccine research. We first outline the key conserved antigenic targets, such as the hemagglutinin (HA) stem, neuraminidase (NA), and matrix proteins (M2e, NP, and M1), which are crucial for eliciting broad cross-reactive immunity. We then delve into advanced antigen design strategies, including immunofocusing, multi-antigen combinations, computationally optimized broadly reactive antigens (COBRA), and nanoparticle-based platforms. Furthermore, we evaluate evolving vaccine delivery systems, from traditional inactivated and live-attenuated vaccines to modern mRNA and viral vector platforms, alongside the critical role of novel adjuvants in enhancing immune responses. The convergence of these disciplines—structural biology, computational design, and nanotechnology—is driving the field toward a transformative goal. We conclude that the successful development of a universal influenza vaccine will likely depend on the strategic integration of these innovative approaches to overcome existing immunological and logistical challenges, ultimately providing durable and broad-spectrum protection against diverse influenza virus strains. Full article

Caffeoylquinic acids (CQAs), a class of phenolic acid metabolites widely distributed in plants, encompass 15 positional isomers from mono- to tetra-esters, with 5-O-caffeoylquinic acid (5-CQA) as the predominant form. The biosynthesis of 5-CQA from phenylalanine proceeds through five primary pathways, which are finely regulated by environmental, hormonal, and transcription factors from families such as MYB, WRKY, and bHLH. These regulators control 5-CQA synthesis by binding specifically to the promoter regions of key structural genes, including PAL, 4CL and HCT/HQT. Subsequently, 5-CQA serves as a central precursor for the biosynthesis of other CQAs. In terms of bioactivity, CQAs possess remarkable pharmacological activities, encompassing antioxidant, antimicrobial, anti-diabetic, anti-inflammatory and anti-tumor properties. For instance, anti-inflammatory effects are demonstrated by the ability of 5-CQA to reduce key pro-inflammatory cytokines (e.g., TNF-α and IL-1β) and downregulate the TLR4/NF-κB pathway. The synergistic action of 5-CQA with ultraviolet-A reduced succinate-coenzyme Q reductase activity by approximately 72%, highlighting its potential to disrupt bacterial metabolism and combat antibiotic resistance. Furthermore, 3,4,5-triCQA exhibits potent anti-influenza virus activity, potentially through a mechanism distinct from existing neuraminidase inhibitors. Beyond medicine, CQAs show promise in light industry. They serve as antibiotic alternatives in livestock feed to enhance gut health, extend food shelf life through their antioxidant activity, and function as active ingredients in UV-protective skincare formulations. CQAs also enhance plant stress tolerance to cold, arsenic, and pests by mechanisms such as scavenging reactive oxygen species and inhibiting pest mobility. While this review consolidates progress in the biosynthesis and bioactivity of CQAs specifically with caffeoyl substituents, future efforts should leverage modern biotechnological tools and interdisciplinary approaches to bridge critical knowledge gaps in their biosynthesis, transport, and clinical translation. Full article

Avian influenza viruses (AIVs) of H10 subtype are able to circulate in domestic and wild bird populations but can also spill over and adapt to mammals, posing a continuous risk to biodiversity conservation, veterinary health, and public health. In the present study, we assessed the zoonotic potential of nine H10 AIVs isolated from waterbirds during surveillance and research studies carried out in Italy between 1994 and 2007. Overall, six H10NX strains from wild mallards (n. 1 H10N2, n. 5 H10N7), one H10N7 strain from domestic mallards, and two H10N8 strains from Eurasian coots were sequenced by next-generation sequencing (NGS). HA phylogenetic analysis indicated a marked divergence between viruses from these two sympatric waterbird species and showed a close relationship between three H10N7 strains from wild mallard and one H10N7 isolate of domestic origin. Sequence analysis revealed the presence of several molecular markers, associated with increased zoonotic potential, including the PB2-A588V mutation found in the Eurasian coot H10N8 viruses and previously linked to mammalian adaptation in H10 strains. Molecular analysis also showed that all H10 viruses were susceptible to the major approved classes of influenza antivirals (inhibitors of neuraminidase, matrix-2, and polymerase acid protein). Moreover, phenotypic assay confirmed their susceptibility to oseltamivir and zanamivir drugs. From an ecological perspective, we found that different H10 gene pools seem to be harboured in different waterbird species sharing the same environment; additionally, a bidirectional transmission of H10 mallard isolates occurred between natural and anthropic ecosystems. Overall, our findings account for the need of continuous monitoring of AIVs belonging to the H10 subtype. Full article

Bovine parainfluenza virus type 3 (BPIV3) is a significant pathogen implicated in bovine respiratory disease complex (BRDC), leading to lung tissue destruction, immunosuppression, and subsequent bacterial infections in cattle, hence incurring considerable economic losses globally. Notwithstanding its importance, a limited number of commercial vaccinations are presently accessible. The fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, as protective antigens of the Paramyxoviridae family, can elicit neutralizing antibodies and are regarded as optimal candidates for the creation of genetically modified vaccines. A multi-epitope-based peptide vaccine (MEBPV) was developed by immunoinformatics methodologies by choosing epitopes from the F and HN proteins characterized by high antigenicity, moderate toxicity, and limited allergenic potential. The epitopes were combined with suitable linkers and adjuvants to produce the vaccine, whose physicochemical qualities, immunological attributes, solubility, and structural stability were improved and evaluated using computational methods. Molecular docking and molecular dynamics simulations demonstrated the strong potential binding affinity and stability of the vaccination with TLR2, TLR3, and especially TLR4 receptors. Immune simulations forecasted strong humoral and cellular responses, accompanied by a significant elevation in interferon-γ (IFN-γ) production. The vaccine sequence was later cloned into the pET-28a (+) vector for possible expression in Escherichia coli. Despite in silico predictions suggesting a favorable immunogenic potential, additional in vitro and in vivo studies are necessary to confirm its protective efficacy and safety. This research establishes a solid foundation for the creation of safe and efficacious subunit vaccines targeting BPIV3 and presents novel perspectives for the formulation of vaccinations against additional viral infections. Full article

Background/Objectives: Influenza A virus undergoes continuous antigenic drift, necessitating annual vaccine reformulation. Saudi Arabia faces unique epidemiological challenges owing to mass gatherings during religious pilgrimages and the dynamic movement of foreign workers. This study aimed to characterize the genetic diversity of hemagglutinin (HA) and neuraminidase (NA) genes of influenza A viruses circulating in Riyadh and to assess their match with vaccine strains during the 2024–2025 period. Methods: Nasopharyngeal samples (n = 363) were collected from patients presenting with influenza-like illness. RT-PCR was used for detection and subtyping. Sequence and phylogenetic analysis of the complete HA and NA gene sequences from A/H1N1pdm09 strains (n = 7) were then performed. Results: Of the 363 samples, 110 (30.3%) were positive for influenza A; among these, 68 (61.8%) were A/H1N1pdm09, and 42 (38.2%) were H3N2. Phylogenetic analysis revealed that all A/H1N1pdm09 strains belonged to clade 5a.1, distinct from vaccine strains. In comparison with the vaccine strain A/Wisconsin/67/2022, seven amino acid substitutions in the HA gene and eight in the NA gene were recorded in Saudi circulating strains. The significant genetic divergence between circulating A/H1N1pdm09 strains and current vaccine strains indicates potential vaccine mismatch. Conclusions: The significant genetic divergence between circulating A/H1N1pdm09 strains and current vaccine strains suggests potential vaccine mismatch. Continuous surveillance programs along with vaccination plans are necessary to tackle the changing influenza A virus strains in the special epidemiological context of Saudi Arabia. Full article

The emergence of drug-resistant influenza virus strains necessitates the development of novel antiviral agents with unique mechanisms of action. This study presents the synthesis and in vitro evaluation of a new class of antiviral compounds: sodium salts of amino acid ester conjugates based on the closo-dodecaborate anion [B₁₂H₁₂]²⁻, linked via a tetrahydropyran-derived spacer (Na₂[B₁₂H₁₁O(CH₂)₆C(O)X], where X = L-Trp-OMe (Na₂2); L-His-OMe (Na₂3); L-Met-OMe (Na₂4); Pld-OMe (Na₂5)). The antiviral activity was assessed against contemporary, multidrug-resistant influenza A virus strains, including A/Cheboksary/125/2020 (H1N1)pdm09 and A/IIV-Orenburg/83/2012 (H1N1)pdm09. Cross-platform comparison revealed that the dodecaborate-tryptophan conjugate Na₂2 exhibited comparable efficacy to its lead decaborate analog against the Orenburg strain while demonstrating potent activity (IC₅₀ = 5.0 µg/mL) against the Cheboksary strain with reduced susceptibility to neuraminidase inhibitors (oseltamivir; zanamivir) and complete resistance to M2 channel blockers. The histidine-based conjugate Na₂3 also showed significant efficacy against the Cheboksary strain, while methionine and lactam derivatives (Na₂4; Na₂5) remained inactive. This work confirms boron clusters as versatile platforms for antiviral development and establishes structure–activity relationships crucial for optimizing both B₁₀ and B₁₂-based therapeutics against resistant influenza strains. Full article

Sialic acids are terminal monosaccharides that cap glycans on glycoconjugates. Accumulating clinical and experimental evidence shows that obesity, insulin resistance, and diabetes are accompanied by changes in sialic-acid levels. In these conditions, the sialic-acid axis is also broadly remodeled: writers (sialyltransferases), erasers (neuraminidases), and readers (Siglecs) are dysregulated across adipose tissue, liver, pancreas, endothelium, and blood, shifting insulin signaling and inflammatory tone. This review summarizes relevant studies from the perspectives of disease clinical indicators, molecular mechanisms, and interventions targeting sialic acid. Taken together, these results confirm that sialic acids and related molecules play important roles in multiple metabolic diseases; however, controversies remain due to differences in glycan structure, isoforms, and tissue specificity, particularly regarding the precise roles of neuraminidases. Future studies should build on advanced, standardized glycomic and glycoproteomic measures to define molecule- and tissue-specific roles of sialic acids in metabolic disease, enabling reliable biomarkers and guiding targeted therapy. Full article

The Goose/Guandong lineage of highly pathogenic avian influenza virus [A/Goose/Guangdong/1/1996(H5N1)] is the progenitor of the currently circulating Eurasian-lineage highly pathogenic avian influenza H5N1 clade 2.3.4.4b and has been the most consequential highly pathogenic avian influenza lineage globally. Despite increased reports of infections, the extent of exposure and role of wild mammals in the ecology and transmission dynamics of the virus remains poorly understood. We surveyed wild mammals in Ohio, United States to investigate the potential spillover of highly pathogenic H5N1 avian influenza clade 2.3.4.4b. While no active infections—defined as positive results indicative of viral replication and potential propagation—were detected by swab-based molecular tests, serological assays revealed antibodies against multiple avian influenza virus antigens in raccoons and opossums. Specifically, antibodies to avian influenza virus nucleoprotein were detected in 54.9% (n = 61) of samples using enzyme-linked immunosorbent assay; antibodies to Eurasian-lineage highly pathogenic avian influenza H5 clade 2.3.4.4b and North American low pathogenic avian influenza H5 were detected in 43.2% (n = 48) and 22.5% (n = 25) of samples, respectively, using virus neutralization assays; and antibodies to avian influenza virus neuraminidase were detected in 44.1% (n = 49) of samples using enzyme-linked lectin assay. All seropositive animals were sampled at Ohio marshes with previously confirmed highly pathogenic avian influenza H5N1 detections in waterfowl. These findings suggest prior exposure of wild mammals to these viruses without mortality events. Wild mammals may play an intermediary role in the mammalian adaptation of avian influenza A viruses. Therefore, ongoing surveillance of wild mammals is crucial for assessing the risk to public health. Full article

During China’s 41st Antarctic research expedition, samples were collected from wildlife on the Fildes Peninsula, South Shetland Islands, Antarctica. Real-time RT-PCR screening confirmed H5N1 positivity, representing the first identification of the virus in brown skuas on the Fildes Peninsula. Whole-genome sequences obtained from positive samples via next-generation sequencing were subjected to phylogenetic and phylogeographic analyses. The results revealed that these Antarctic strains are most closely related to H5N1 viruses circulating in South America, particularly from Peru and Chile, suggesting a likely introduction via avian migration routes. Furthermore, a unique 17-amino-acid deletion was identified in the stalk region of the neuraminidase (NA) gene, which is uncommon among globally sampled clade 2.3.4.4b variants. This study confirms the arrival of HPAI H5N1 in the Antarctic continent and underscores the necessity for enhanced surveillance to understand the viral ecology and potential risks within this unique ecosystem. Full article

Background: One of the primary strategies for preventing and reducing infectious diseases is vaccination. There are numerous licensed vaccinations of various kinds that can prevent viral infection by triggering the immune system’s reaction to specific antigens beforehand. To elicit a stronger immune response, however, two elements of the immune system—humoral and cellular immunity—should be addressed. Since they target proteins that are difficult to alter, recent innovative techniques for vaccine delivery systems—such as liposomes, nanogels, microemulsions, etc.—have shown excellent immunogenicity qualities. Methods: PubMed, ScienceDirect, and Google Scholar were used as the databases for literature search, and keywords such as “Virosomes”, “Hemagglutinin”, and “IRIV” were selected to ensure relevant articles were included. Results: This article examines a cutting-edge method called virosomes, which are an effective way to deliver pharmaceutically active ingredients that target a variety of illnesses and ailments, as well as vaccines. This resulted from the fact that virosomes possess numerous structural characteristics that might trigger sophisticated immune reactions by utilizing the inactivated virus’s envelope or by imitating it through recombinant methods. Conclusions: Here, we will walk you through the history of virosome development, explore various manufacturing techniques, provide an overview of the latest patents, and conclude with the potential for more virosomal revolutions. Full article

Four new compounds and three new natural products (1−7), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (8–10), were isolated from rice medium cultures of a sponge-associated Penicillium sp. SCSIO41035. The structural elucidations, including the determination of absolute configurations, were accomplished by comprehensive analyses utilizing NMR spectroscopy, HRESIMS, optical rotation data, X-ray crystallography experiments and electronic circular dichroism calculations. Differential NMR signals between symmetric units in cyclotetrapeptides 1 and 2 arise from the asymmetric solution conformations as investigated through conformational searching and theoretical calculations. The asymmetric conformations were primarily caused by the flexibility of the tyrosine residue’s phenyl side chain, with its substantial electron density significantly influencing the NMR signals of nearby groups. Bioactivity screening results displayed that isolated compounds demonstrated good neuraminidase inhibitory activity, with inhibition rates ranging from 43.16% to 85.40% at a concentration of 100 µg/mL. Full article

Background/Objectives: Antigenic drift of influenza A(H1N1pdm09) viruses has led to periodic replacement of vaccine strains. Understanding how structural differences in glycoproteins influence immune protection is crucial for improving vaccine effectiveness. Methods: We conducted a structural analysis of the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from drifted A(H1N1)pdm09 strains: A/South Africa/3626/2008 and A/Guangdong–Maonan/SWL1/2020, as well as their cold-adapted live attenuated vaccine (LAIV) reassortant strains (A/17/South Africa/2013/01(H1N1)pdm09 and A/17/Guangdong–Maonan/2019/211(H1N1)pdm09). We compared their replication in chicken embryo and mammalian cell culture, assessed type I interferon induction, and evaluated post-vaccine protection in mice after homologous and heterogeneous viral challenges. Results: The two vaccine strains had distinct glycosylation patterns for HA and NA. However, they had similar replication capacity in embryonated egg and mammalian cells. In the mouse respiratory tract, both strains replicated similarly. A/17/South Africa/2013/01(H1N1)pdm09 induced significantly higher levels of IFN-α and Mx1 in vitro, and it elicited earlier IgM and IgG response after vaccination in mice. At day 6 after immunization, it provided 70% protection from homologous challenge. A/17/Guangdong–Maonan/2019/211(H1N1)pdm09 did not prevent death, but it reduced viral titer in the lungs. Interestingly, A/17/South Africa/2013/01(H1N1)pdm09 provided full protection from heterologous H5N1 challenge, while A/17/Guangdong–Maonan/2019/211(H1N1)pdm09) only provided partial protection. Conclusions: Differences in HA and NA glycans among A(H1N1)pdm09 strains may influence innate and adaptive immunity, as well as cross-protection. These findings emphasize the importance of glycoprotein structure when selecting vaccine candidates for optimal homologous and cross-protection against influenza. Full article

Four human sialidases (hNEUs, E.C 3.2.1.18) have been identified. Each is an exosialidase identified as either NEU1, NEU2, NEU3, or NEU4. They exhibit differences in structure, subcellular distribution, substrate specificity, and the diseases with which they are associated. Similarly, microbial sialidases (NAs) may catalyze the release of sialyl residues from the same sialoglycoconjugates as hNEUs, even though they have low sequence homology with human NEUs. Use of sequence homology, plus the crystalline structure of human NEU2, has provided researchers with the basis for developing inhibitors that may differentiate between them. While microbial-induced diseases that use sialidase to complete their infectious cycle have been the driving force behind interrogation of possible NA inhibitors, errors affecting expression of functional hNEUs and their correlation with clinical problems has led to study of the sialidases per se. Information gained about sialidase structure, function, mechanism of action, mutations affecting expression, and their role(s) in disease, has provided the information about the different sialidases needed for development of specific therapies. Full article

H5N1 Influenza A virus continues to pose a significant zoonotic threat, with increasing evidence of interspecies transmission and genetic adaptation. Previous studies primarily focused on avian or human isolates, with limited comprehensive analysis of H5N1 evolution across multiple mammalian hosts. Existing molecular surveillance often lags behind viral evolution; this study underscores the necessity for real-time monitoring of ongoing mutations affecting pathogenicity and transmissibility. Our goals are (1) to retrieve and analyze HA, NP and NA gene sequences of H5N1 Influenza A virus from diverse hosts, including humans, poultry and multiple mammalian species, to assess genetic diversity and evolutionary patterns and (2) to evaluate positive selection sites across the three major genes (HA, NP and NA) to determine adaptive mutations linked to host adaptation and viral survival. To achieve these goals, in this study, we considered (78 HA), (62 NP) and (61 NA) gene sequences from diverse hosts, including humans, poultry and multiple mammalian species, retrieved from the NCBI database. Phylogenetic analysis revealed distinct clade formations, indicating regional spread and cross-species transmission events, particularly from avian sources to mammals and humans. Selection pressure analysis identified positive selection across all three genes, suggesting adaptive mutations contributing to host adaptation and viral survival. Homology modeling and molecular dynamics simulations were performed to generate high-quality structural models of HA, NP and NA proteins, which were subsequently validated using multiple stereochemical parameters. Domain analysis confirmed conserved functional motifs, while protein–ligand docking demonstrated stable interactions at conserved binding sites, despite observed residue substitutions in recent isolates. Earlier research concentrated on HA alone; this study integrates HA, NP and NA genes for a broader understanding of viral evolution and adaptation. These findings highlight ongoing evolutionary changes in H5N1 genes that may enhance viral adaptability and pathogenicity, underscoring the need for continuous molecular surveillance and updated antiviral strategies. Full article

Human parainfluenza viruses 3 (hPIV3) are important pathogens, responsible for acute respiratory tract diseases, especially in young children. Information on hPIV3 circulation and their diversity pattern in Russia is limited. The aim of this study was to perform a molecular and genetic characterization of hPIV3 circulating in Saint Petersburg, Russia. From October 2017 to September 2023, 14,704 swabs were screened using real-time reverse transcription-PCR. A phylogenetic analysis of the complete hemagglutinin–neuraminidase (HN) gene was performed. Out of 1334 positive hPIV cases, hPIV3 was the most common subtype. Phylogenetic analysis of the studied and previously published HN sequences revealed four distinct genetic clusters, A, B, C, and D, with Cluster D being first delineated in this study. In addition, two newly subdivided genetic lineages, C5a and C5b, were documented. Phylogenetic analysis revealed that the analyzed Russian strains grouped into Cluster C and D; further subclusters C5a, C5b, C3b, C3e, and C3a. While three strains were classified within cluster D, the majority of isolates fell within subcluster C3a, followed by C5b. Taken together, these findings demonstrate the co-circulation of hPIV3 strains during the study period. This is the first study that describes the genetic and molecular aspects of hPIV3 circulating in Russia. Moreover, our results provide an up-to-date hPIV3 phylogenetic analysis. Full article