Search Results (138)

Crimean–Congo hemorrhagic fever virus (CCHF-V) and Ebola virus are lethal pathogens that cause widespread outbreaks of hemorrhagic fever. Both diseases can be transmitted through contact with the bodily fluids of infected individuals, but as an arbovirus, CCHF-V is primarily transmitted through tick bites. Both of these viruses are classified as Risk Group 4 due to the appreciable health threat they pose. To date, there are few effective treatments available to combat these deadly hemorrhagic fevers. Consequently, identifying and characterizing ion channels (viroporins) encoded in the viral genomes may lead to potential targeted drug development. Therefore, using bacteria-based genetic assays, two viroporin candidates from CCHF-V and Ebola have been examined, and their proposed structures have been modeled to aid in further drug discovery. The results indicate that CCHF-V-gp exhibits channel activity, which is indistinguishable from established viroporins found in other viruses. In contrast, our experimental approach was unable to uncover a viroporin candidate in the Ebola virus. Full article

With the popularization of social media, information related to public health events has seen explosive growth online, making it essential to accurately identify informative tweets with decision-making and management value for public health emergency response and risk monitoring. However, existing methods often suffer performance degradation during cross-event transfer due to differences in data distribution, and research specifically targeting public health events remains limited. To address this, we propose the Label Confusion Domain Adversarial Network (LCDAN), which innovatively integrates label confusion with domain adaptation to enhance the detection of informative tweets across different public health events. First, LCDAN employs an adversarial domain adaptation model to learn cross-domain feature representation. Second, it dynamically evaluates the importance of different source domain samples to the target domain through label confusion to optimize the migration effect. Experiments were conducted on datasets related to COVID-19, Ebola disease, and Middle East Respiratory Syndrome public health events. The results demonstrate that LCDAN significantly outperforms existing methods across all tasks. This research provides an effective tool for information detection during public health emergencies, with substantial theoretical and practical implications. Full article

Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC₅₀. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article

In this paper, we introduce a fast iterative scheme and establish its convergence under a contractive condition. This new scheme can be viewed as an extension and generalization of existing iterative schemes such as Picard–Noor and UO iterative schemes for solving nonlinear equations. We demonstrate theoretically and numerically that the new scheme converges faster than several existing iterative schemes with the fastest known convergence rates for contractive mappings. We also analyze the stability of the new scheme and provide numerical computations to validate the analytic results. Finally, we implement the new scheme in MATLAB R2023b to simulate the dynamics of the Ebola virus disease. Full article

Ebola virus (EBOV) causes severe disease outbreaks in humans with high case fatality rates. EBOV requires adaptation to cause lethal disease in mice by acquiring single mutations in both the nucleoprotein (NP) and VP24 genes. As an attempt to model mouse-adapted EBOV (MA-EBOV), we engineered novel pentacistronic minigenomes (5xMG) containing a reporter gene, VP40, and glycoprotein genes as well as the NP and VP24 genes from either EBOV or MA-EBOV. The 5xMGs were constructed and optimized, and the produced transcription- and replication-competent virus-like particles (trVLPs) were demonstrated to infect several cell lines. Introduction of the mouse-adaptation mutations did not significantly impact the replication and transcription of the 5xMG or the relative infectivity of the trVLPs in vitro. This work demonstrates the development of the 5xMG system as a new versatile tool to study EBOV biology. Full article

This paper studies the effects of resource limitations, immunity decay, and delays on an Ebola epidemic model and an optimal control strategy. The model includes two types of delays: a delay in the incubation period of infected individuals and a delay in treatment. Conditions for a Hopf bifurcation at the endemic equilibrium are verified, with its direction and stability analyzed via normal form theory and the center manifold theorem. We also studied the optimal control problem for the SIRD delay model using educational campaigns and Ebola survivors’ immunity as control variables. Furthermore, we formulate an optimization problem based on Pontryagin’s maximum principle. This problem uses a modified Runge-Kutta approach with delays to discover the best control strategy to reduce infections and intervention costs. Finally, simulation results confirm analytical conclusions and show the practical implications of the optimum Ebola control plan using the dde23 MATLAB R2024a built-in solver and DDE-Biftool. Full article

The COVID-19 pandemic has underscored the need for effective and affordable antiviral drugs. Anthropogenic activities have increased interactions among humans, animals, and wildlife, contributing to the emergence of new and re-emerging viral diseases. RNA viruses pose significant challenges due to their rapid mutation rates, high transmissibility, and ability to adapt to host immune responses and antiviral treatments. The World Health Organization has identified several diseases (COVID-19, Ebola, Marburg, Zika, and others), all caused by RNA viruses, designated as being of priority concern as potential causes of future pandemics. Despite advances in antiviral treatments, many viruses lack specific therapeutic options, and more importantly, there is a paucity of broad-spectrum antiviral drugs. Additionally, the high costs of current treatments such as Remdesivir and Paxlovid highlight the need for more affordable antiviral drugs. Cyclic peptides from natural sources or designed through molecular modeling have shown promise as antiviral drugs with stability, low toxicity, high target specificity, and low antiviral resistance properties. This review emphasizes the urgent need to develop specific and broad-spectrum antiviral drugs and highlights cyclic peptides as a sustainable solution to combat future pandemics. Further research into these compounds could provide a new weapon to combat RNA viruses and address the gaps in current antiviral drug development. Full article

Phenomenological models are highly effective tools for forecasting disease dynamics using real-world data, particularly in scenarios where detailed knowledge of disease mechanisms is limited. However, their reliability depends on the model parameters’ structural and practical identifiability. In this study, we systematically analyze the identifiability of six commonly used growth models in epidemiology: the generalized growth model (GGM), the generalized logistic model (GLM), the Richards model, the generalized Richards model (GRM), the Gompertz model, and a modified SEIR model with inhomogeneous mixing. To address challenges posed by non-integer power exponents in these models, we reformulate them by introducing additional state variables. This enables rigorous structural identifiability analysis using the StructuralIdentifiability.jl package in JULIA. We validated the structural identifiability results by performing parameter estimation and forecasting using the GrowthPredict MATLAB Toolbox. This toolbox is designed to fit and forecast time series trajectories based on phenomenological growth models. We applied it to three epidemiological datasets: weekly incidence data for monkeypox, COVID-19, and Ebola. Additionally, we assessed practical identifiability through Monte Carlo simulations to evaluate parameter estimation robustness under varying levels of observational noise. Our results confirm that all six models are structurally identifiable under the proposed reformulation. Furthermore, practical identifiability analyses demonstrate that parameter estimates remain robust across different noise levels, though sensitivity varies by model and dataset. These findings provide critical insights into the strengths and limitations of phenomenological models to characterize epidemic trajectories, emphasizing their adaptability to real-world challenges and their role in informing public health interventions. Full article

The recombinant vesicular stomatitis virus-Zaire Ebolavirus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP) was highly effective against Ebola virus disease in a ring vaccination trial conducted during the 2014–2016 outbreak in Guinea and is licensed by regulatory agencies including US FDA, EMA, and prequalified by WHO. Vaccination studies in a nonhuman primate (NHP) model guided initial dose selection for clinical trial evaluation. We summarize two dose-ranging studies with the clinical-grade rVSVΔG-ZEBOV-GP vaccine candidate to assess the impact of dose level on immune responses and efficacy in an NHP Ebola virus (EBOV) challenge model. Forty-six cynomolgus macaques were vaccinated with a wide range of rVSVΔG-ZEBOV-GP doses and challenged 42 days later intramuscularly with 1000 pfu EBOV. Vaccination with rVSVΔG-ZEBOV-GP induced relatively high levels of EBOV-specific IgG and neutralizing antibodies, measured using the same validated assays as used in rVSVΔG-ZEBOV-GP clinical trials. Similar responses were observed across dose groups from 1 × 10⁸ to 1 × 10² pfu. A single vaccination conferred 98% protection from lethal intramuscular EBOV challenge across all dose groups. These results demonstrate that robust antibody titers are induced in NHPs across a wide range of rVSVΔG-ZEBOV-GP vaccine doses, correlating with high levels of protection against death from EBOV challenge. Full article

The rVSVΔG-ZEBOV-GP vaccine demonstrated efficacy in preventing Ebola virus (EBOV) disease in a ring vaccination clinical trial conducted during the 2014–2016 West Africa outbreak and is licensed by regulatory agencies, including the US FDA and the EMA. Here, we present two studies that evaluated the durability of immunogenicity and protection from an EBOV challenge up to ~12 months following vaccination with rVSVΔG-ZEBOV-GP in nonhuman primates (NHPs). Cynomolgus macaques were vaccinated with either one or two doses of rVSVΔG-ZEBOV-GP or a saline control and were challenged intramuscularly with EBOV at a target dose of 1000 pfu at ~4 months (Study 1) or ~8 or ~12 months (Study 2) after the last vaccination. All vaccinated animals developed robust ZEBOV-GP-specific IgG and neutralizing antibody titers, which were sustained until the last time point tested prior to the challenge. The majority of animals (88–93%) challenged with EBOV at ~4 or ~8 months post-vaccination survived, whereas the survival rate was lower (53%) in animals challenged ~12 months post-vaccination. These results demonstrate that both one-dose and two-dose regimens of the rVSVΔG-ZEBOV-GP vaccine induced durable ZEBOV-GP-specific antibody titers in NHPs and provided high levels of protection against a lethal EBOV challenge up to ~8 months post-vaccination. In this stringent challenge model, decreased protection was observed at ~12 months post-vaccination despite sustained antibody levels. Full article

Algal lectin Griffithsin (GRFT) is a well-known mannose-binding protein which has broad-spectrum antiviral activity against several important infectious viruses including HIV, HCV, and SARS-CoV-2. Therefore, GRFT has been brought great attention to antiviral therapeutic development. In this report, we have tested GRFT’s activity against the lethal Ebola virus in vitro and in vivo. Our data have shown that the IC₅₀ value is about 42 nM for inhibiting Zaire Ebola virus (EBOV) infection in vitro. The preliminary in vivo mice model using mouse-adapted EBOV has also shown a certain efficacy for delayed mortality compared to the control animals. A GRFT pull-down experiment using viral particles demonstrates that GRFT can bind to N-glycans of EBOV. Thus, it can be concluded that GRFT, through binding to viral glycans, may block Ebola virus infection and has potential for the treatment of Ebola virus disease (EVD). Full article

The Ebola virus (EBOV), a highly lethal pathogen causing hemorrhagic fever, poses a persistent public health threat, with devastating multi-organ complications and high transmission potential through bodily fluids. EBOV’s pathogenesis is marked by severe oxidative stress and immune dysregulation, where increased reactive oxygen species (ROS) levels foster cellular damage, hinder immune defenses, and facilitate viral replication. Through immune evasion and suppression of cellular stress responses, EBOV affects both innate and adaptive immunity, activating pyroptosis, PANoptosis, necroptosis, and lymphocyte apoptosis, thereby amplifying inflammation and disease severity. Recent research suggests that bioactive molecules, including quercetin, curcumin, eugenol, and p-anisaldehyde, may offer therapeutic potential due to their antioxidant, anti-inflammatory, and immunomodulatory effects. This review also underscores the potential of conventional treatments, including amiodarone, favipiravir, remdesivir, azithromycin, chloroquine, and nitazoxanide, as therapeutic agents against EBOV, thanks to their antiviral and anti-inflammatory properties, although their efficacy varies across experimental models. These natural compounds could enhance immune resilience by scavenging ROS, modulating inflammation, and mitigating immune dysregulation, presenting promising adjunctive strategies to support conventional EBOV therapies. Full article

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model. Full article

The Ebola virus (EBOV) causes severe disease in humans, and animal models are needed to evaluate the efficacy of vaccines and therapeutics. While non-human primate (NHP) and rodent EBOV infection models have been well characterized, there is a growing need for an intermediate model. Here, we provide the first report of a small-particle aerosol (AE) EBOV ferret model and disease progression compared with the intramuscular (IM) EBOV ferret model. EBOV infection of ferrets by either route resulted in uniform lethality in 5–6.5 days post infection (dpi) in a dose-dependent manner, with IM-infected ferrets succumbing significantly earlier than AE-infected ferrets. EBOV disease progression differed between AE and IM routes, with significant viremia and presence of virus in target organs occurring earlier in the AE model. In contrast, significant fever, clinical signs of disease, liver pathology, and systemic inflammation occurred earlier in the IM EBOV model. Hepatocellular damage and splenic pathology were noted in both models, while pronounced lung pathology and renal impairment were exclusive to the AE and IM models, respectively. These results demonstrate that small-particle AE and IM ferret EBOV models share numerous common features with NHP and human EBOV infection by these routes and will therefore be useful for the development of vaccine and therapeutic countermeasures. Full article

Ebola virus (EBOV) is one of three filovirus members of the Orthoebolavirus genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR^−/−) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR^−/− mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans. Full article