Viral Components Research Articles

Essential role of the interaction between classical swine fever virus core protein and cellular MYO1B in viral components transport to exosomes and titer maintenance

Classical swine fever (CSF) is a severe disease caused by the highly contagious CSFV. Our previous study demonstrated that exosomes from CSFV-infected cells contained significant amounts of viral genome and Core (C) protein and were infectious. To further elucidate the mechanisms underlying the formation of these infectious exosomes, we investigated the intracellular transport of the C protein in this study. We first identified the synchronized transport of the C protein and viral genome to exosomes, distinguishing it from other structural proteins. This suggests that the C protein likely binds to the viral genome and is transported to exosomes as a nucleocapsid. Subsequently, Co-IP and co-localization experiments confirmed the interaction between the host Myosin 1B (MYO1B) protein and the C protein. Key interaction sites were identified by generating and analyzing various C protein point mutations and truncation variants. The results indicate that specific sites at the N-terminus of the C protein significantly impact its interaction with MYO1B. Ultimately, by modulating MYO1B expression, we found that MYO1B knockdown significantly reduced the C protein and viral genome content in exosomes, leading to a decrease in CSFV titers. These findings underscore the critical role of MYO1B in facilitating the transport of the C protein and viral genome into exosomes during CSFV infection. Overall, this study explores the mechanism of infectious exosome formation during CSFV infection, revealing the critical role of the host MYO1B in this process. This is the first study to identify the involvement of MYO1B in viral infection, not only offering important insights into host-virus interactions but also identifying a new target for antiviral drug development.

Lymphocytic choriomeningitis arenavirus utilises intercellular connections for cell to cell spread

The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane. Consistent with this, we visualized abundant actin- and tubulin-rich connections conjoining LCMV-infected and uninfected cells within cultures, resembling tunnelling nanotubes (TNTs). Within these TNT-like connections, confocal and STED microscopy identified puncta containing the major structural components of LCMV virions alongside genomic RNA, consistent with intercellular transit of assembled virions or ribonucleoprotein genome segments. Blocking the extracellular route of infection by adding potent LCMV neutralising antibody M28 to supernatants during infection revealed around 50% of LCMV transmission was via intercellular connections. These results show arenaviruses transmission is more complex than previously thought involving both extracellular and intercellular routes.

A theoretical systems chronopharmacology approach for COVID-19: Modeling circadian regulation of lung infection and potential precision therapies.

The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the urgent need for innovative therapeutic approaches. Recent studies have revealed a complex interplay between the circadian clock and SARS-CoV-2 infection in lung cells, opening new avenues for targeted interventions. This systems pharmacology study investigates this intricate relationship, focusing on the circadian protein BMAL1. BMAL1 plays a dual role in viral dynamics, driving the expression of the viral entry receptor ACE2 while suppressing interferon-stimulated antiviral genes. Its critical position at the host-pathogen interface suggests potential as a therapeutic target, albeit requiring a nuanced approach to avoid disrupting essential circadian regulation. To enable precise tuning of potential interventions, we constructed a computational model integrating the lung cellular clock with viral infection components. We validated this model against literature data to establish a platform for drug administration simulation studies using the REV-ERB agonist SR9009. Our simulations of optimized SR9009 dosing reveal circadian-based strategies that potentially suppress viral infection while minimizing clock disruption. This quantitative framework offers insights into the viral-circadian interface, aiming to guide the development of chronotherapy-based antivirals. More broadly, it underscores the importance of understanding the connections between circadian timing, respiratory viral infections, and therapeutic responses for advancing precision medicine. Such approaches are vital for responding effectively to the rapid spread of coronaviruses like SARS-CoV-2.

Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose-response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.IMPORTANCEA significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both in vitro and in vivo and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.

Claudin2 is involved in the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells

The genus Megalocytivirus, belonging to the family Iridoviridae, is one of the most detrimental virus groups to fish aquaculture. Megalocytivirus creates a virus-mock basement membrane (VMBM) on the surface of infected cells. This membrane provides attachment sites for lymphatic endothelial cells (LECs), disrupting fish's endothelial cell-extracellular matrix system. This disruption triggers injury to the vascular system and can result in death. Exploring the VMBM-cell interaction mechanism is crucial for uncovering the pathogenesis of Megalocytivirus and identifying therapeutic targets. Claudins, a class of tetra transmembrane proteins, play a key role in creating tight junctions between endothelial or epithelial cells. In this study, we demonstrated that the expression of Claudin2, a member of the Claudin family in fish, was significantly up-regulated by Megalocytivirus infection. Claudin2 was found in LECs attached to the surface of infected cells. It interacted with the VMBM viral components VP23R, VP08R, and VP33L at multiple binding sites through its two extracellular loops. However, it did not interact with the host basement membrane’s nidogen. Therefore, Claudin2 is involved in the interaction of LEC with VMBM and plays a role in the disturbed distribution of extracellular matrix and endothelial cells in Megalocytivirus-infected fish tissues. This study aims to uncover the molecular mechanisms by which Megalocytivirus infection leads to pathological changes in the vascular system.

A State-of-the-Art Review on the Recent Advances in Exosomes in Oncogenic Virus.

Oncogenic viruses are responsible for approximately 12% of human malignancies, influencing various cancer processes through intricate interactions with host cells. Exosomes (EXOs), nanometric-sized microvesicles involved in cell communication, have emerged as critical mediators in these interactions. This review aims to explore the mechanisms by which EXOs produced by cells infected with oncogenic viruses promote cancer growth, enhance viral transmissibility, and act as immunomodulators. A comprehensive review was conducted, focusing on recent studies highlighting the mechanisms by which EXOs facilitate the oncogenic potential of viruses. The analysis included the characterization of exosomal content, such as microRNAs (miRNAs) and proteins, and their effects on tumor microenvironments and immune responses. A search was performed using databases including PubMed, ScienceDirect, and Google Scholar. MeSH keywords related to EXOs, oncogenic viruses, and cancer were used to retrieve relevant review, systematic, and research articles. Findings indicate that EXOs from oncogenic virus-infected cells carry viral components that facilitate infection and inflammation. These EXOs alter the tumor microenvironment, contributing to the development of virus-associated cancers. Additionally, the review highlights the growing interest among researchers regarding the implications of EXOs in cancer progression and their potential role in enhancing the oncogenicity of viruses. The findings underscore the pivotal role of EXOs in mediating the oncogenic effects of viruses, suggesting that targeting exosomal pathways may provide new therapeutic avenues for managing virus-associated cancers. Further research is needed to fully elucidate the functional mechanisms of EXOs in viral oncogenesis.

Collaborative study on the cross-reactivity of two influenza B viral components in single radial immunodiffusion assay using quadrivalent influenza vaccines in Japan from 2015/16 to 2021–22 influenza season

A quadrivalent influenza vaccine (QIV) has been available in Japan since the 2015/2016 influenza season. Single radial immunodiffusion (SRID) assays are currently used worldwide to measure the hemagglutinin (HA) content of influenza vaccine components because they are simple, accurate, and the regulatory requirement, ensuring consistency in manufacture for the HA content. However, the cross-reactivity of antisera against the two lineages of the influenza B virus (IFVB) may cause inaccurate quantification of HA content in QIVs using the SRID assay. To examine cross-reactivity and develop an appropriate procedure for accurate measurement of vaccine potency, a collaborative study with four Japanese vaccine manufacturers was conducted to measure the HA contents of trivalent influenza vaccines (TIVs) and QIVs by SRID assay with a single and a mixture of reference antigens (refAgs) from each lineage of IFVB for seven influenza seasons from 2015/16 to 2021/22. The cross-reactivity of the two IFVB components in the SRID assay varied depending on the vaccine viruses. Our study demonstrated that it is useful to validate a suitable combination for each refAg and reference antiserum by selecting the combination showing similar HA contents between experimental TIV and QIV before lot release testing.

Coxsackievirus B3-Induced m6A Modification of RNA Enhances Viral Replication via Suppression of YTHDF-Mediated Stress Granule Formation.

N6-methyladenosine (m6A) is the most prevalent internal RNA modification. Here, we demonstrate that coxsackievirus B3 (CVB3), a common causative agent of viral myocarditis, induces m6A modification primarily at the stop codon and 3' untranslated regions of its genome. As a positive-sense single-stranded RNA virus, CVB3 replicates exclusively in the cytoplasm through a cap-independent translation initiation mechanism. Our study shows that CVB3 modulates the expression and nucleo-cytoplasmic transport of the m6A machinery components-METTL3, ALKBH5 and YTHDFs-resulting in increased m6A modifications that enhance viral replication. Mechanistically, this enhancement is mediated through YTHDF-driven stress granule (SG) formation. We observed that YTHDF proteins co-localize with human antigen R (HuR), a protein facilitating cap-independent translation, in SGs during early infection. Later in infection, YTHDFs are cleaved, suppressing SG formation. Notably, for the first time, we identified that during early infection CVB3's RNA-dependent RNA polymerase (3D) and double-stranded RNA (dsRNA) are stored in SGs, co-localizing with HuR. This early-stage sequestration likely protects viral components for use in late-phase replication, when SGs are disrupted due to YTHDF cleavage. In summary, our findings reveal that CVB3-induced m6A modifications enhance viral replication by regulating YTHDF-mediated SG dynamics. This study provides a potential therapeutic strategy for CVB3-induced myocarditis.

The actin-binding protein palladin associates with the respiratory syncytial virus matrix protein.

The respiratory syncytial virus (RSV) matrix (M) protein plays an important role in infection as it can interact with viral components as well as the host cell actin microfilaments. The M-actin interaction may play a role in facilitating the transportation of virion components to the apical surface, where RSV is released. We show that M protein's association with actin is facilitated by palladin, an actin-binding protein. Cells were infected with RSV or transfected to express full-length M as a green fluorescent protein (GFP)-tagged protein, followed by removal of nuclear and cytosolic proteins to enrich for cytoskeleton and its associated proteins. M protein was present in inclusion bodies tethered to microfilaments in infected cells. In transfected cells, GFP-M was presented close to microfilaments, without association, suggesting the possible involvement of an additional protein in this interaction. As palladin can bind to proteins that also bind actin, we investigated its interaction with M. Cells were co-transfected to express GFP-M and palladin as an mCherry fluorescent-tagged protein, followed by cytoskeleton enrichment. M and palladin were observed to colocalize towards microfilaments, suggesting that palladin is involved in the M-actin interaction. In co-immunoprecipitation studies, M was found to associate with two isoforms of palladin, of 140 and 37 kDa. Interestingly, siRNA downregulation of palladin resulted in reduced titer of released RSV, while cell associated RSV titer increased, suggesting a role for palladin in virus release. Together, our data show that the M-actin interaction mediated by palladin is important for RSV budding and release.IMPORTANCERespiratory syncytial virus is responsible for severe lower respiratory tract infections in young children under 5 years old, the elderly, and the immunosuppressed. The interaction of the respiratory syncytial virus matrix protein with the host actin cytoskeleton is important in infection but has not been investigated in depth. In this study, we show that the respiratory syncytial virus matrix protein associates with actin microfilaments and the actin-binding protein palladin, suggesting a role for palladin in respiratory syncytial virus release. This study provides new insight into the role of the actin cytoskeleton in respiratory syncytial virus infection, a key host-RSV interaction in assembly. Understanding the mechanism by which the RSV M protein and actin interact will ultimately provide a basis for the development of therapeutics targeted at RSV infections.

Entry of Newcastle disease virus into host cells: an interplay among viral and host factors.

Newcastle disease (ND) is a major burden for the poultry industry worldwide, especially in developing countries. The virus that causes this disease, Newcastle disease virus (NDV), is also an effective vector for the development of novel human and animal vaccines and a promising oncolytic virus for cancer therapy. The mechanism of entry of NDV into host cells is of particular interest because it has a significant impact on the infectivity, host range, and pathogenicity of the virus. Here, we present an overview of the entry of NDV into cells, focusing on the interplay among viral and host factors involved in this process. In particular, recent research revealing novel features of NDV attachment to cells, the identification of viral and cellular components that regulate binding of the virus to cells, and the emerging role of novel cellular routes of NDV entry are discussed. More importantly, some of the remaining gaps in our understanding of NDV entry and some fundamental questions for research efforts in the future are also highlighted.

Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization.

Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies.

Alterations of the gut microbiome in HIV infection highlight human anelloviruses as potential predictors of immune recovery

BackgroundHIV-1 infection is characterized by a massive depletion of mucosal CD4 T cells that triggers a cascade of events ultimately linking gut microbial dysbiosis to HIV-1 disease progression and pathogenesis. The association between HIV infection and the enteric virome composition is less characterized, although viruses are an essential component of the gut ecosystem. Here, we performed a cross-sectional analysis of the fecal viral (eukaryotic viruses and bacteriophages) and bacterial microbiome in people with HIV (PWH) and in HIV-negative individuals. To gain further insight into the association between the gut microbiome composition, HIV-associated immunodeficiency, and immune recovery, we carried out a longitudinal study including 14 PWH who initiated antiretroviral therapy (ART) and were followed for 24 months with samplings performed at baseline (before ART) and at 2, 6, 12, and 24 months post-ART initiation.ResultsOur data revealed a striking expansion in the abundance and prevalence of several human virus genomic sequences (Anelloviridae, Adenoviridae, and Papillomaviridae) in stool samples of PWH with severe immunodeficiency (CD4 < 200). We also noted a decreased abundance of sequences belonging to two plant viruses from the Tobamovirus genus, a reduction in bacterial alpha diversity, and a decrease in Inoviridae bacteriophage sequences. Short-term ART (24 months) was linked to a significant decrease in human Anelloviridae sequences. Remarkably, the detection of Anellovirus sequences at baseline independently predicted poor immune recovery, as did low CD4 T cell counts. The bacterial and bacteriophage populations were unique to each PWH with individualized trajectories; we found no discernable pattern of clustering after 24 months on ART.ConclusionAdvanced HIV-1 infection was associated with marked alterations in the virome composition, in particular a remarkable expansion of human anelloviruses, with a gradual restoration after ART initiation. In addition to CD4 T cell counts, anellovirus sequence detection might be useful to predict and monitor immune recovery. This study confirms data on the bacteriome and expands our knowledge on the viral component of the gut microbiome in HIV-1 infection.3oR8qDfXoWY9s_P5ES648YVideo

Identification of multiple novel viruses in bar-headed goose feces from Tibet of China.

The bar-headed goose is a typical high-altitude bird that primarily inhabits alpine lakes and wetlands in Central Asia, with a remarkable ability to adapt to high elevations. Previous studies have shown that they can be infected with parasites such as Cryptosporidium spp. At present, there were few reports on its infection with the virus. In this study, we utilized viral metagenomics to conduct a detailed analysis of the viral components in the fecal samples of bar-headed geese (Anser indicus) from the Tibet region of China. Multiple novel viruses were identified including four novel astroviruses, four novel caliciviruses, ten novel circoviruses, and nineteen novel parvoviruses. Among them, four astroviruses shared the highest amino acid sequence identities of 63.45-99.47% with different avastrovirus strains. Four caliciviruses and ten circoviruses were identified as unclassified caliciviruses and unclassified circoviruses, separately. Nineteen parvoviruses clustering into four groups maybe four different novel species of the genus Chaphamaparvovirus. These newly discovered viruses have potential implications for the health of avian species, particularly bar-headed geese. This study not only helps us understand the health status of bar-headed geese, but also offers crucial genomic information for future disease prevention and treatment strategies.

Detection of H1N1 Influenza Virus in the Bile of a Severe Influenza Mouse Model.

Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood. We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection. Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.

Prenatal immune activation in rats and adult exposure to inescapable shocks reveal sex-dependent effects on fear conditioning that might be relevant for schizophrenia

Prenatal infection is considered a relevant factor for neurodevelopmental alterations and psychiatric diseases. Administration of bacterial and viral components during pregnancy in rodents results in maternal immune activation (MIA), leading to schizophrenia-like neurochemical and behavioral changes. Despite some evidence for abnormal fear conditioning in schizophrenia, only a few animal studies have focused on this issue. Therefore, we addressed the impact of the administration of the viral mimetic polyI:C to pregnant Long-Evans rats on the adult offspring response to inescapable shocks (IS) and contextual fear conditioning. In males, polyI:C induced a greater endocrine (plasma ACTH) response to IS and both polyI:C and IS enhanced fear conditioning and generalization to a completely different novel environment (hole-board), with no additive effects, probably due to a ceiling effect. In contrast, a modest impact of polyI:C and a lower impact of IS on contextual fear conditioning and generalization was observed in females. Thus, the present results demonstrate that polyI:C dramatically affected fear response to IS in adult males and support the hypothesis that males are more sensitive than females to this treatment. This model might allow to explore neurobiological mechanisms underlying abnormal responsiveness to fear conditioning and stressors in schizophrenia.

The Assembly of HTLV-1-How Does It Differ from HIV-1?

Retroviral assembly is a highly coordinated step in the replication cycle. The process is initiated when the newly synthesized Gag and Gag-Pol polyproteins are directed to the inner leaflet of the plasma membrane (PM), where they facilitate the budding and release of immature viral particles. Extensive research over the years has provided crucial insights into the molecular determinants of this assembly step. It is established that Gag targeting and binding to the PM is mediated by interactions of the matrix (MA) domain and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This binding event, along with binding to viral RNA, initiates oligomerization of Gag on the PM, a process mediated by the capsid (CA) domain. Much of the previous studies have focused on human immunodeficiency virus type 1 (HIV-1). Although the general steps of retroviral replication are consistent across different retroviruses, comparative studies revealed notable differences in the structure and function of viral components. In this review, we present recent findings on the assembly mechanisms of Human T-cell leukemia virus type 1 and highlight key differences from HIV-1, focusing particularly on the molecular determinants of Gag-PM interactions and CA assembly.

Soluble markers of viral rebound and post-treatment HIV control.

We focus on the different classes of biological molecules measurable in easily accessible bodily fluids that have the potential to serve as biomarkers for the HIV post-treatment controller (PTC) phenotype and/or the timing of viral rebound after stopping antiretroviral therapy (ART). Various viral components and host factors measurable in body fluids can play crucial roles in understanding and predicting the PTC phenotype. We review recent findings linking viral components, the quantitative and qualitative features of antibodies (including autologous HIV-specific antibodies), markers of inflammation and tissue damage, other host proteins (including hormones such as sex hormones), as well as metabolites, extracellular vesicles, and cell-free DNA to HIV control post-ART interruption. Several of these molecules can or have the potential to predict the time and probability of viral rebound after stopping ART and are biologically active molecules that can directly or indirectly (by modulating immune pressures) impact the size and activity of HIV reservoirs during and post-ART interruption. A comprehensive model combining multiple markers is needed to predict the PTC phenotype. This model can be leveraged to predict and understand the PTC phenotype, which can guide novel curative interventions to replicate this phenotype in post-treatment non-controllers.

Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host's immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.

Co-circulation of seasonal influenza A(H1N1)pdm09, A(H3N2) and B/Victoria lineage viruses with further genetic diversification, EU/EEA, 2022/23 influenza season.

BackgroundInfluenza viruses can cause large seasonal epidemics with high healthcare impact and severity as they continually change their virological properties such as genetic makeup over time.AimWe aimed to monitor the characteristics of circulating influenza viruses over the 2022/23 influenza season in the EU/EEA countries. In addition, we wanted to compare how closely the circulating viruses resemble the viral components selected for seasonal influenza vaccines, and whether the circulating viruses had acquired resistance to commonly used antiviral drugs.MethodsWe performed a descriptive analysis of the influenza virus detections and characterisations reported by National Influenza Centres (NIC) from the 30 EU/EEA countries from week 40/2022 to week 39/2023 to The European Surveillance System (TESSy) as part of the Global Influenza Surveillance and Response System (GISRS).ResultsIn the EU/EEA countries, the 2022/23 influenza season was characterised by co-circulation of A(H1N1)pdm09, A(H3N2) and B/Victoria-lineage viruses. The genetic evolution of these viruses continued and clade 6B.1A.5a.2a of A(H1N1)pdm09, 3C.2a1b.2a.2b of A(H3N2) and V1A.3a.2 of B/Victoria viruses dominated. Influenza B/Yamagata-lineage viruses were not reported.DiscussionThe World Health Organization (WHO) vaccine composition recommendation for the northern hemisphere 2023/24 season reflects the European virus evolution, with a change of the A(H1N1)pdm09 component, while keeping the A(H3N2) and B/Victoria-lineage components unchanged.

Cheminformatics Screening of Phytochemicals Targeting Diverse Potential Receptors to Elicit Antiviral Properties

Objective: Recently, the COVID-19 (coronavirus disease) pandemic caused by SARSCoV-2 (severe acute respiratory syndrome coronavirus) gave rise to a public health emergency worldwide. Similarly, other viruses like HIV (Human Immunodeficiency Virus)/AIDS (acquired immunodeficiency syndrome), Zika, Ebola, and Influenza and their mutants have called for an urgent need for a Broad-spectrum antiviral drug, inhibiting the infection by targeting the common essential components of different viruses. Methods: Based on ancient medicinal knowledge, we made an attempt through molecular docking analysis to explore different phytochemical compounds against well-recognized viral receptors. Results: A total of 29 phytochemicals were virtually examined against 4 targets essential in the life cycle of viral infection: CD147 (Cluster of Differentiation 147), CD209L (Cluster of Differentiation 209 Lectin), eIF4A (Eukaryotic Initiation Factor 4A), and RdRp (RNA-dependent RNA polymerase). Providentially, Berbamine was identified as the best-hit lead molecule based on binding energies, conventional hydrogen bonding numbers, and non-covalent interactions. It exhibited binding energies as -8.3 kcal/mol with CD147, -8.2 kcal/mol with CD209L, -9.5 kcal/mol with eIF4A, and - 10.5 kcal/mol with RdRp. Additionally, in-silico drug likeliness (Lipinski’s rule) and ADME studies depict high bioavailability and gastrointestinal absorption and follow Lipinski’s rule. Conclusion: The data presented by our study exemplify phytochemicals from the selected plants that could target conserved viral components shared across multiple viruses. Berbamine can be designed as a possible drug to target Broad-Spectrum viruses, limiting the effectiveness of different viruses.