Carnivorous sponge–associated iridovirus (CaSpA-IV) is a recently described virus identified in two deep-sea cladorhizid sponge species from the Gulf of Maine and Baffin Bay. To assess its ecological distribution and potential transmission pathways, we molecularly screened for CaSpA-IV in 32 calanoid copepod samples collected across Newfoundland and Labrador coastal and shelf waters, along with 24 mucus swab and tissue samples collected from six individual deep-sea Paragorgia arborea coral colonies, and three seawater samples from the Gulf of Maine. Two P. arborea tissue specimens from different colonies were sequence-confirmed as CaSpA-IV-positive, making this the first detection of an iridovirus in this host. All copepod and seawater samples tested negative. However, calanoid copepods cannot be definitively ruled out as a transmission vector due to limited sampling. These findings demonstrate that CaSpA-IV may infect two invertebrate phyla in geographically distant benthic habitats. Future work should focus on whole-genome sequencing of diverse CaSpA-IVs and targeted sampling of other potential vectors/hosts to elucidate transmission routes and the ecological impact of this virus.
Abstract On November 14th, 2025, the Ethiopian Ministry of Health confirmed the country’s first Marburg virus outbreak, representing another in a series of recent outbreaks across Africa in only 3 years. Marburg virus disease (MVD) is a highly lethal zoonotic haemorrhagic fever caused by the Marburg virus. This review synthesises the current evidence on MVD, covering epidemiology, pathogenesis, diagnostics, and emerging countermeasures, such as investigational antivirals and vaccines. Despite the severity of the disease outcome, no licensed treatment or vaccine exists. Recent outbreaks, including Rwanda (2024), Tanzania and Ethiopia (2025), have accelerated evaluation of investigational therapeutics such as remdesivir and monoclonal antibody MBP091 under expanded access and early‑phase studies; no randomised human efficacy data are currently available for MVD, alongside novel platforms including mRNA and adenovirus-vectored vaccines. Advances in molecular virology have helped to elucidate mechanisms of immune evasion and viral persistence, informing strategies for targeted interventions. Diagnostic capacity and therapeutic deployment remain constrained in resource-limited settings. Strengthening global preparedness will require integrated surveillance, rapid clinical trial frameworks, and equitable access to vaccines and antivirals.
South Africa has demonstrated exceptional capacity for viral detection and genomic analysis, most visibly through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomics and wastewater-based monitoring. Yet outside respiratory virus programmes, the country’s approach to emerging viral infections remains comparatively reactive, pathogen-specific, and biased toward high-visibility events. This Perspective argues that South Africa’s most actionable surveillance blind spot is not only the importation of novel pathogens, but the delayed recognition of transmission already underway within endemic and re-emerging zoonotic and arboviral systems. Using illustrative exemplars-mpox, Crimean–Congo haemorrhagic fever virus, Rift Valley fever virus, and neglected neuroinvasive arboviruses- we propose that “emergence” in South Africa often takes the form of under-diagnosed local amplification rather than dramatic first appearance. We advocate a syndrome-based, diagnostically guided strategy coupled to an integrated One Health “signal-to-action” framework that links clinical syndromes with veterinary events, vector and environmental monitoring, and proportionate laboratory escalation (targeted molecular/serology testing, confirmatory assays, and sequencing when indicated). The objective is not indiscriminate multiplexing, but earlier alignment between ecological risk, clinical suspicion, and test availability- so that outbreak response begins despite tentative early signals and before widespread human infection or the acceleration of the outbreak.
Abstract Hepatitis E virus (HEV) Open Reading Frame 1 (ORF1) encodes a non-structural polyprotein. It has domains of methyl transferase, Y domain, fatty acid binding domain, hypervariable domain, X domain, helicase, and RNA-dependent RNA polymerase. Meta-analysis of virus-host interaction and immunological studies suggested that HEV ORF1 plays a significant role in HEV pathogenesis. Many virus-host interaction studies suggest that potential open reading frame 1 (pORF1) domains interact with host factors involved in various pathways, such as metabolism, innate immune pathways, etc. Interestingly, many in vitro studies showed that the mutations in ORF1 regions alter the virus replication efficiency in cell culture; this suggests the importance of ORF1 in virus pathogenesis. Similarly, the genome sequence analysis of HEV-infected patients reveals that specific amino acid mutations in ORF1 contribute to the disease severity. Studies have empirically proven the association of specific ORF1 mutations in fulminant hepatitis failure (FHF) patients and their effects on HEV replication efficiency using reverse genetic systems. These ORF1 amino acid mutations enhance viral fitness and likely contribute to poor clinical outcomes. Additionally, genotype-specific mutations show different pathogenic significance, contributing to differences in disease outcomes across HEV genotypes. In summary, apart from its role in virus replication, the ORF1 protein interacts with various host factors and contributes to pathogenesis. Mutations in ORF1 are one of the factors that contribute to the development of FHF in HEV-infected patients. This review summarises literature on pORF1 and its role in HEV pathogenesis.
The emergence of new zoonotic viruses such as SARS-CoV has been a concern for public health since the 1990s. The latest COVID-19 outbreak has proven to be a devastating threat not only to human survival but also to national economies in the 21st century. This outbreak has underscored the necessity for enhanced risk assessment and surveillance of zoonotic diseases, demanding increased attention from the government and stakeholders. Despite the COVID-19 outbreak being contained in several countries, the threat of other emerging viruses still exists. Indonesia, home to extensive biodiversity, including one of the world’s largest bat populations, represents a recognized hotspot for viral emergence. Rapid population growth, land-use change, deforestation, wildlife-livestock-human interface expansion, cultural practices, and climate-driven ecological shifts further increase the likelihood of zoonotic spillover events. Despite these risks, viral surveillance in Indonesia remains limited, resulting in under-detection of zoonotic threats. This review synthesizes current evidence, comprehensive landscape on key virus groups of concern in Indonesia, including Coronaviridae, Paramyxoviridae, Orthomyxoviridae (avian influenza virus), Flaviviridae, Filoviridae, Hantaviridae, Rhabdoviridae (lyssavirus), Herpesviridae, Poxviridae (monkeypox virus), Reoviridae, and Hepeviridae (hepatitis E virus). We highlight their prevalence, reservoir hosts, ecological drivers, challenges, and opportunities for improved surveillance to enhance early detection and mitigate future pandemic threats.
Ticks are parasites of a wide range of animal species and the main vectors of many viruses of health concern. However, a genome-scale characterization of tick diversity in Italy remains lacking, although several areas of the country are known to be affected by tick-borne viral infections. To begin addressing this important knowledge gap, we sequenced 22 tick transcriptomes from three different locations along a north-south gradient in Italy. We found that viral richness, prevalence, and abundance varied among samples. In our dataset, northern populations showed a higher presence of viruses of potential health concern; however, given the unbalanced and temporally split sampling design, these observations should be interpreted with caution. Using a combination of metagenomics and phylogenomics, we recovered 99 viral contigs, which were assembled into 89 uncultivated viral genomes (UViGs), as some viral species possess segmented genomes composed of multiple contigs. These 89 UViGs correspond to 31 viral operational taxonomic units, including 10 new putative species (i.e., unclassified viruses) and 19 species reported in Italy for the first time. We present the updated phylogenies of viruses of known or new potential zoonotic concern including Haseki tick virus, members of the Orthototiviridae and Phenuiviridae families, Tick-borne encephalitis virus, and four different phleboviruses (Brown dog tick phlebovirus 2, Norway phlebovirus 1, Leuven phlebovirus and Tick phlebovirus). These results increase our general understanding of the evolution of tick-borne viruses, provide a comprehensive look at their diversity in Italy, and represent a source of information for implementing future surveillance activities.
Dengue virus (DENV), a mosquito-borne flavivirus, establishes persistent infections in Aedes vectors, yet the mechanisms underlying viral persistence and potential genomic integration remain poorly understood. Here, we established in vitro models using Aedes albopictus C6/36 and Aedes aegypti Aag2 cells to investigate DENV-1-derived viral DNA (vDNA) formation and integration. Our results demonstrated that vDNA production is initiated at Day 3 postinfection in C6/36 cells and Day 5 in Aag2 cells, revealing cell-specific temporal dynamics in vDNA generation. Importantly, we detected DENV-1 vDNA in wild-caught Ae. albopictus from Guangzhou, confirming its presence in natural mosquito populations. To further explore viral integration, we constructed genome walking libraries for both cell lines and employed genome walking combined with high-throughput sequencing, which provided direct evidence of DENV-1 sequence integration into the Ae. albopictus genome. These findings not only elucidate the kinetics of vDNA production in mosquito cells but also highlight the potential role of vDNA in facilitating viral genome integration, offering new insights into the long-term host–pathogen interactions and the evolutionary dynamics of arboviruses in their vectors. This study advances our understanding of DENV persistence mechanisms and highlights the need to further investigate the biological implications of viral integration in mosquito populations.
Respiratory viral infections remain a major global health challenge, underscored by seasonal influenza, respiratory syncytial virus (RSV), and the COVID-19 pandemic. Although vaccines and antiviral drugs are central to control strategies, their effectiveness can be limited by viral evolution, resistance, and delayed development. CRISPR-based antivirals have emerged as a programmable approach to directly target viral genomes or host factors required for infection. This review summarizes current CRISPR strategies for respiratory viruses, focusing on RNA-targeting systems such as Cas13 and DNA-targeting approaches, including Cas9 and Cas12. We synthesize evidence from preclinical studies in cell culture, primary human airway models, and animal lungs, highlighting how guide design, multiplex targeting, and conserved viral regions can limit viral escape. We also discuss key translational challenges, including pulmonary delivery, biodistribution, off-target profiling, immune responses, and regulatory considerations. Finally, we outline future directions, including integration with antimicrobial peptides, rapid viral genotyping, and combination therapies. Together, this review provides a practical assessment of what CRISPR antivirals can realistically offer for respiratory viral infections and identifies the critical steps needed to advance these approaches toward clinical use.
Livestock suffer from several bacterial infections leading to various ailments, including the respiratory, reproductive, systemic, and mainly the enteric diseases; which result not only into a major decline in their productivity, but also a great financial loss on a global scale. The current treatment measures for most of these bacterial infections constitute mainly the antibiotics. However, an extensive use of antibiotics in the past few years, has resulted in the origin and spread of mutant bacterial strains exhibiting multiple resistance against most of the available antibiotics, many of these mutants acquiring the capability of forming biofilms that hinder drug penetration. This global increase in antibiotic resistance has necessitated the need for the search for alternative treatment measures to combat infectious diseases in livestock. Bacteriophage or “phage therapy” is a viable alternative approach in this direction, as the phages are not only host-specific- targeting specific bacteria without having any adverse effect on the beneficial microflora, but also have the potential to be effective in penetration of biofilm layer formed by the resistant bacteria. Further, phages are ubiquitous, and can be easily isolated from soil, sewage, water bodies, food products, humans and animal skin, saliva, stool etc.; thus, increasing the likelihood of finding a large variety of phage isolates having the potential to be used as antimicrobials against different infectious agents. Phage therapeutics includes monophage therapy, which involves the application of a single phage; phage cocktail therapy, which utilizes multiple phages; or the use of genetically altered phages. The present paper discusses the potential of phage therapy as an alternative for antibiotics to control bacterial infections in livestock, different forms in which it can be applied, as well as identifying key challenges that are currently preventing its widespread clinical use and successful implementation.
Abstract Dengue fever is a significant community health problem in tropical regions such as Bangladesh, where it is difficult to diagnose early because it has similar symptoms to other febrile illnesses. Confirmatory tests are frequently non-existent in resource-limited settings, increasing the necessity for tools that utilize common clinical data as a means of relieving healthcare load. This paper presents a proof-of-concept case study using the Tree-Augmented Naive Bayes (TAN) Bayesian network to detect dengue using complete blood count (CBC) features. We analysed a publicly available, fully de-identified dataset from a single center in Jamalpur, Bangladesh, comprising 1523 patients tested for dengue and other febrile illnesses, with 19 hematological and demographic variables. Probabilistic modeling and clinical alignment involved the discretization of variables. The Boruta algorithm was used to choose nine significant predictors. TAN has been compared against Naive Bayes, Support Vector Machine, Logistic Regression, Linear Discriminant Analysis, and K-Nearest Neighbour using tenfold cross-validation. TAN achieved high sensitivity (0.961) but relatively low specificity (0.314), with moderate balanced accuracy (0.637) and AUC-ROC (0.671), indicating its suitability as a screening and decision-support tool rather than a definitive diagnostic model. Its directed acyclic graph expresses relationships among such variables as platelet count, hematocrit, and leukocyte differentials and provides better probabilistic information than independence-based models. Key technical limitations of this proof-of-concept study include single-center data, discretization of continuous variables, class imbalance, and lack of external validation, all of which are documented in the manuscript’s Limitations section. TAN showed strong sensitivity, although its specificity was limited, making it more suitable for use in unbalanced or uncertain diagnostic settings. In conclusion, this proof-of-concept case study demonstrates that TAN is an interpretable and high-sensitivity dengue detection algorithm that uses available CBC data within a single resource-limited setting. The primary contribution is clinical interpretability and feasibility, not generalizable deployment. Prospective multi-center validation is required before clinical application.
Dengue fever, caused by the Dengue virus (DENV), is a significant global health concern that affects millions of people each year, and there is currently no specific antiviral treatment available. The RNA-dependent RNA polymerase (RdRp) is an essential viral enzyme that replicates the viral RNA genome, making it a crucial target for therapeutic intervention. Previous computational studies have primarily focused on small natural or synthetic compound libraries, often relying solely on docking or limited validation, resulting in low chemical diversity and structural novelty. In this study, we employed a computational approach to identify a novel natural product inhibitor of DENV RdRp. High-throughput virtual screening of 407,270 natural compounds from the COCONUT database was performed to identify four lead compounds: CNP0243663, CNP0306108, CNP0384605, and CNP0226892, which were selected based on favourable binding free energies ranging from − 81.64 to − 74.97 kcal/mol. The selected compounds showed higher docking scores, ranging from − 9.639 to − 11.806 kcal/mol, compared to the co-crystallized reference inhibitor 68 T, which had a docking score of − 9.368 kcal/mol. Molecular docking and interaction analysis revealed that the selected compounds bind to key residues within the RdRp active sites, demonstrating higher binding affinities and more favourable interaction profiles than 68 T. Additionally, these selected compounds were further optimized using Density Functional Theory (DFT) and subjected to 200 ns Molecular Dynamics (MD) simulations, confirming their stable binding and protein–ligand interactions. Post-MD analysis, including Molecular Mechanics and Generalized Born Surface Area (MM/GBSA) rescoring and Principal Component Analysis (PCA), further validated their conformational stability and dynamic behaviour. These results provide novel computational insights into natural compounds as promising RdRp inhibitors, offering a prioritized set of lead candidates for the development of anti-dengue therapeutics and establishing a robust foundation for future experimental validation.
Phage therapy, treating bacterial infections with bacteriophages, is complicated. Phages are probably the most diverse entity on Earth, closely followed by bacteria, and both are involved in the treatment of diverse infections in humans, everyone with different immune response. Overall, this causes variation that makes treatment design difficult to navigate. The key to how clinical treatments should be implemented lies in the selection of phages, measures to avoid the emergence of phage resistance in the bacteria, reducing negative immunological reactions and understanding the treatment as a complex kinetic process. The aim of this article is to discuss common obstacles and present concrete measures to improve the results of phage therapy based on the nature of phages and bacteria, as well as with the aid of mathematical modelling.
Abstract Dengue virus affects millions of people annually, particularly in tropical and subtropical regions where Aedes mosquitoes serve as primary vectors. Conventional control measures face limitations due to pesticide resistance, environmental concerns, and issues of host specificity. Molecular approaches offer promising alternatives, supported by growing knowledge of dengue viral genomics and protein structures, which underpins the development of antiviral therapeutics and vector-control strategies. Advances in RNA interference, CRISPR-Cas9 systems, gene-drive technologies, paratransgenesis, and Wolbachia-based interventions demonstrate notable potential for reducing dengue transmission. This review examines current molecular strategies and the related aspects of dengue pathogenesis that inform their application. While these innovations show substantial promise, they also present challenges, including high costs, extended development timelines, and ethical considerations. Ongoing research aims to balance these benefits and limitations to support sustainable long-term management of dengue.
The increasing identification of novel parvoviruses in swine has raised questions about their role in multifactorial syndromes like PMWS. This study used PCR to investigate the presence of porcine parvovirus 4 (PPV4), porcine bocavirus 1 (PBoV1), and porcine bocavirus 3 (PBoV3) in tissue and serum samples from pigs with or without PMWS in Brazil. PPV4 was significantly associated with PMWS, showing a six-fold higher frequency of DNAemia in affected animals (41.2
Foot and mouth disease (FMD) is a highly contagious viral infection that continues to threaten global livestock health, with profound effects on animal productivity, rural livelihoods, food security, and international trade. Caused by the foot and mouth disease virus (FMDV), the infection comprises seven immunologically distinct serotypes: O, A, C (now considered extinct), Asia1, SAT1, SAT2, and SAT3, with no cross-protection among them. This antigenic diversity complicates vaccine formulation and outbreak control, particularly in endemic regions. Recent resurgences in countries such as South Africa highlight persistent gaps in surveillance and response capacity. This review examines the global synthesis of serotype diversity, transmission dynamics and socioeconomic impacts of foot and mouth disease and control, highlights critical research gaps, and proposes integrated mitigation approaches. Literature was sourced from major academic databases and supplemented with gray literature from relevant international organizations (WOAH, FAO, OIE-WAHIS). Transmission occurs mainly through direct contact with infected animals via saliva, nasal secretions, milk, semen, and vesicular fluid. Indirect and airborne routes also contribute significantly, with the virus surviving for extended periods in cool, moist environments. Contaminated animal products pose further risks to trade and biosecurity. The disease disrupts milk production, impairs mobility, and results in major economic losses. Effective control requires regionally tailored, multifaceted strategies encompassing enhanced biosecurity, next-generation vaccines, robust surveillance systems, and strengthened international collaboration. Integrated interventions against FMD can bolster animal health, food system resilience, and global trade security.
Chandipura virus (CHPV), a neurotropic arbovirus belonging to the Rhabdoviridae family, is linked to recurring outbreaks of acute encephalitis disease in India, primarily affecting children and exhibiting significant mortality rates. Despite its considerable public health impact, specialised antiviral treatments and approved vaccines are lacking, highlighting the urgent need for experimental models to further pathogenesis and therapeutic research. This review thoroughly analyses the current animal models used in CHPV research, highlighting their significance in clarifying viral tropism, immunological responses, and disease mechanisms. Laboratory mice, especially neonates and juvenile animals with underdeveloped blood-brain barriers, have demonstrated optimal suitability, mirroring the age-dependent vulnerability and neuropathological characteristics observed in humans. Research employing murine models has elucidated the mechanisms of CHPV neuroinvasion, immune modulation, and oxidative stress–mediated neuronal injury, while also facilitating preclinical evaluation of recombinant vaccines, siRNA-based antivirals, and therapeutic agents such as minocycline and favipiravir. In contrast, other animal species, including domestic and laboratory animals, exhibit subclinical infection with seroconversion but no overt disease, limiting their experimental relevance. This review underscores the essential role of murine models in CHPV research, while emphasizing the necessity for improved, physiologically relevant systems to more accurately replicate natural infection dynamics and expedite vaccine and treatment development.
Lassa fever, caused by the Lassa virus (LASV), remains a major public health threat in West Africa, characterized by recurrent outbreaks, high mortality rates, and significant socio-economic impact. The lack of a licensed vaccine and challenges of traditional vaccine development for this Biosafety Level 4 pathogen call for innovative, safe, and effective approach to identify vaccine candidates against LASV. In this study, an integrated reverse vaccinology approach was employed to design a multi-epitope subunit vaccine targeting the conserved L protein of LASV. Linear and conformational B-cell epitopes, cytotoxic T-lymphocyte (CTL; MHC-I) epitopes, and helper T-lymphocyte (HTL; MHC-II) epitopes were predicted using established servers. The epitopes were rigorously filtered and assembled into a chimeric vaccine construct using appropriate linkers and an N-terminal adjuvant. The construct was evaluated and predicted to be antigenic, non-allergenic, hydrophilic, and soluble. Structural modelling and validation confirmed good physicochemical properties of the vaccine candidate. Docking revealed stable interaction with TLR4; immune simulation predicted robust activation of CD4 + and CD8 + T-cells, a Th1-polarized cytokine profile (IFN-γ, IL-2), and a lasting memory response; while population coverage analysis indicated broad global and West African coverage. The vaccine construct targets cell-mediated immunity critical for protection against LASV while its unique sequence features suggest potential self-adjuvanting properties. While its predicted instability may require formulation strategies, the vaccine construct demonstrates strong preclinical promise. Hence, it was concluded that the vaccine is represent a novel and computationally validated multi-epitope candidate designed LASV to elicit potent and durable immune responses, providing a solid foundation for downstream experimental evaluation.
Antibody kinetics following SARS-CoV-2 infection differs from the classical trajectory, where infection initially elicits IgM responses before subsequent class-switching to IgG and IgA, complicating the use of IgM as a marker of recent SARS-CoV-2 infection. This atypical pattern may reflect cross-reactive memory responses against highly-related human coronaviruses (HCoV). Here, we investigated the interplay between early IgG, IgM, and IgA responses to SARS-CoV-2 infections and HCoV antibody responses. Serum IgM, IgA, and IgG responses against the spike (S) of four HCoVs; and the S, nucleocapsid (N), and receptor binding domain (RBD) of SARS-CoV-2 were quantified by a multiplex immunoassay in acute SARS-CoV-2 cases (N = 51) 0–14 days post onset and pre-pandemic controls (N = 30). SARS-CoV-2 IgG levels and percent seropositivity were higher at 0–7 days compared to controls, increasing further at 8–14 days. Beta-HCoV IgA, IgG, and IgM were higher in cases than controls, increasing between 0 and 7 and 8–14 days. Among early (0–7 days) SARS-CoV-2 S IgG responders, IgG levels correlated positively with beta-HCoV S IgG (HCoV-HKU1: R = 0.62, P = 0.023 and HCoV-OC43: R = 0.81, P < 0.001) for IgG. High SARS-CoV-2 S IgM among infected individuals correlated positively with HCoV S IgM levels. SARS-CoV-2 infection elicits cross-reactivity across IgM, IgG, and IgA responses to HCoVs, suggesting limitations in the use of IgM as a serological marker of recent infection. These findings highlight the complexity of immune responses to SARS-CoV-2 and the importance of accounting for potential cross-reactivity to related viruses when investigating serological markers of infection and assessing correlates of protection.
Hepatitis B virus (HBV) has defied cure and is responsible for hepatocellular carcinoma and liver cirrhosis. In view of this, literatures were searched for structures of hepatitis viruses, their family, genotype, shape, genome size, weight, diameter, radius, area, volume, and infectivity with intent to assessing their morphometric, metabolic and structural parameters for determination of pathogenicity, infectivity, mutability for therapeutic, immunogenic and psychogenic consequences. HBV could undergo rotation, reflection, and translation for evasion of therapy and vaccination. Findings have shown that icosahedral shape of HBV with angles (54), triangles (18), faces (20), edges (30) and vertices (12) could pose challenges of antigenic shift and drift. Meanwhile large genome size of HAV (7.5 kb), HCV (9.6 kb), HEV (7.2 kb) and HGV (9.4 kb) and low metabolism constant could limit their pathogenicity. However, HBV may be very active with reduced number of viruses in the host cells and may defy treatment and immunization. Combination of two or more anti-HBV drugs when the viral load has declined can eliminate the virus. HAV, HBV, and HCV can cause psychiatric illness alone or with HIV. All the hepatitis viruses and their seroconversions portend high or higher risk of pathogenicity and virulence because of their antigenic shift and drift, which may be morphometric and structure-dependent. Therefore, tremendous variations in the morphometry and structure of the viruses should be expected in near or far future, if holistic therapeutic and vaccination measures are not emphasized.
The demographics of HIV study participants do not represent the global epidemic: women and minoritised ethnicities are underrepresented. This single-centre retrospective cohort study identified that clinic-level study participation was diverse, differing from prevailing trends. Gender and identifying as MSM (man-who-has-sex-with-men) were not associated with participation. Male participants were younger and more recently diagnosed. Participation in certain ethnicities surpassed the 4.3
