Search Results (323)

A secreted protein toxin encoded by a satellite dsRNA-enabled dissection of the genetic control of replication and expression of a single-segment dsRNA virus, the first Totivirus, L-A. Among the then-novel findings were i. “head-full replication”, ii. a supposedly forbidden “T = 2” capsid symmetry based on an asymmetric dimer, iii. a host N-acetyltransferase whose modification of the coat protein is necessary for packaging, iv. Kex1 and Kex2 pro-toxin peptidases leading to discovery of the pre-pro-insulin processing enzymes, and v. specific viral (+) strand sites/structures needed for RNA packaging and (-) strand synthesis. L-A viral (+) strands made in the particle are extruded to the cytoplasm. Those destined for translation are 5′ 7meGMP-capped by a coat protein activity that steals the cap from cellular mRNAs. (+) strands destined for encapsidation in new coats are not capped. Three host-encoded anti-viral systems were found, one based on blocking translation of the viral non-polyA mRNAs (Ski2,3,8 complex), another a 5′->3′ exoribonuclease specific for uncapped molecules (such as the viral (+) strands)(Ski1/Xrn1), and the third a mitochondrial nuclease released in cells undergoing meiosis/sporulation (Nuc1). All of these systems protect cells from virus-induced pathology and have clear animal homologs. The 3′ polyA of yeast mRNAs is dispensable for translation in ski2Δ slh1Δ cells, and such cells are healthy unless the L-A and M dsRNAs are present, suggesting that this polyA is primarily a device allowing cells to distinguish viral and cellular mRNAs. We suggest that the ribosome-associated Ski2,3,8 proteins block 60S subunit joining on polyA⁻ mRNAs. Recent evidence of roles for other cellular components controlling viral expression and replication suggests that yeast viruses will continue to be a fertile area for study of viral pathogenesis and host anti-viral systems. Full article

Chalcones are naturally occurring open-chain flavonoids widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Their versatile scaffold allows for extensive structural modifications, leading to a diverse range of natural and synthetic derivatives with notable biological potential. In the context of viral infections, chalcones have demonstrated remarkable efficacy against a variety of human pathogens, including dengue virus, HIV, HCV, influenza A, SARS-CoV-2, and other emerging viruses. Beyond human health, several chalcones have shown potent activity against plant viruses such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV), and animal viruses including porcine reproductive and respiratory syndrome virus (PRRSV) and mammalian reovirus (MRV), underscoring their broad antiviral spectrum. These compounds act through multiple mechanisms, including the inhibition of viral enzymes (e.g., proteases, polymerases, and integrases), interference with viral entry and replication, and the modulation of host-related pathways. Recent advances in molecular docking, structure–activity relationship (SAR) studies, and synthetic optimization have further highlighted chalcones as a promising scaffold for antiviral drug discovery. Accordingly, this review summarizes and categorizes antiviral chalcones reported over the last two decades, emphasizing and critically discussing their molecular targets, mechanisms of action, and pharmacological potential as lead compounds. It also provides a comparative perspective on their pharmacological relevance by correlating their activities against standard therapeutic agents and reference inhibitors. Furthermore, the most recurrent viral targets were critically discussed regarding their conservation, expected genetic barriers to resistance, and the global SAR trends identified for the corresponding antiviral chalcones. Finally, in silico ADMET profiling of the most promising naturally occurring chalcones was performed to evaluate their drug-likeness and pharmacokinetic properties, offering guidance for future structural optimization and translational development. Collectively, these findings highlight the chalcone scaffold as a versatile platform for the development of novel antiviral agents targeting diverse viral and host pathways. Full article

Mammarenaviruses are enveloped, ambisense, single-stranded RNA viruses capable of causing fatal hemorrhagic fevers and severe neurological disorders in humans. Although muroid rodents have historically been recognized as the primary reservoirs for major pathogens like Lassa virus, recent surveillance has revealed a significant expansion of their host range. This review aims to synthesize current global data regarding the epidemiology of mammarenaviruses in conventional reservoirs and the emergence of novel arenaviruses in non-traditional mammalian hosts. To achieve this, we comprehensively analyzed recent molecular and metagenomic surveillance data, evolutionary studies, and epidemiological reports published worldwide. Key discoveries include Wenzhou virus in Asian house shrews, Plateau Pika virus in plateau pikas, and an independent, geographically clustered of hedgehog-associated arenaviruses across Europe. Ultimately, this review underscores the global distribution of these pathogens and the critical need for continued, multi-host surveillance worldwide. Full article

Seashore paspalum (Paspalum vaginatum), a salinity-tolerant turfgrass, lacks well-characterized viral profiles. This study reports the discovery of a novel virus, tentatively named Paspalum latent virus (PaLV), representing a new taxon within the Alphaflexiviridae. Using high-throughput sequencing and RACE PCR, the 6995 nt genome was determined, revealing five open reading frames. Notably, PaLV lacks the AlkB domain and exhibits unique features, including overlapping start-stop codons (ORF4/ORF5) and a second in-frame AUG in the coat protein (CP) region. Phylogenetic analysis of the replicase placed PaLV in a distinct clade, separate from Potexvirus and Lolavirus. Despite low sequence identity, AlphaFold2 revealed conserved CP structural domains. Genetic analysis of 11 isolates showed low diversity and strong purifying selection. Pathogenicity assays through mechanical transmission demonstrated a broad but latent host range, including Zea mays and Sorghum spp. These findings suggest PaLV represents a novel species within a putatively new genus, Paspalovirus. Given its 90% incidence rate and latent profile, the RT-PCR assay developed here is vital for routine molecular diagnostics in turfgrass management and germplasm conservation. Full article

Dengue is the most common vector-borne viral disease worldwide, posing an increasing global health threat. Despite its high burden, no approved antiviral treatments or widely applicable vaccines exist, and patient management remains limited to supportive care, underscoring the urgent need for antiviral development. The NS5 protein is a prime antiviral target, owing to its crucial role in viral replication, high conservation across dengue virus (DENV) serotypes and lack of a human orthologue. We conducted a comprehensive sequence-to-structure analysis to identify conserved druggable regions within NS5, integrating large-scale sequence analysis with structural characterization across all four DENV serotypes. We identified four highly promising Consensus Druggable Pockets within the NS5 dimer—CDP1d, CDP3d, CDP5d and CDP12d—that overlap functionally critical regions, alongside 149 new potential hot spot residues. Domain-specific analysis revealed that MTase offers more densely conserved targets, whereas RdRp provides broader druggable surfaces, revealing complementary features for pharmacological modulation. Several identified pockets spatially overlap known inhibitor binding sites, and preliminary docking analyses support their capacity to accommodate small molecules, reinforcing their therapeutic relevance as candidate targets. Collectively, these findings provide a robust framework for the rational design of pan-serotype anti-DENV NS5 antivirals with an enhanced barrier to resistance. Full article

Bovine adenovirus (BAdV) is associated with respiratory and enteric diseases in cattle. In this study, the complete genomic sequence of a novel BAdV strain (named BAdV/LN/CHN/2023) was sequenced and annotated using the next-generation sequencing (NGS) technology. The viral genome comprises 32,391 base pairs with a GC content of 44.93%, encoding 33 predicted open reading frames (ORFs), consistent with the genomic organization of mastadenoviruses. Comparative genomic analysis confirmed that BAdV/LN/CHN/2023 contains conserved structural and functional motifs characteristic of the genus Mastadenovirus. Phylogenetic analysis revealed that BAdV/LN/CHN/2023 shares low similarity with all currently recognized bovine mastadenoviruses classified by the International Committee on Taxonomy of Viruses (ICTV). In addition, an open reading frame (ORF) encoding the 146R protein was annotated in this strain; this feature has not been identified in any previously recognized bovine mastadenoviruses. This study presents the first full-length genomic sequence of a putative BAdV-11 strain, and based on ICTV criteria, we propose that this strain represents a novel mastadenovirus species, supported by phylogenetic distance and genomic divergence. Our findings expand the known genetic diversity of BAdVs and contribute to a better understanding of their evolutionary relationships. Full article

Enteroviruses are positive-sense single-stranded RNA viruses and common pathogens that are responsible for diverse public health diseases. To facilitate the study of the virus biology and pathogenesis of enterovirus, we developed a rapid method for construction of the enteroviral cDNA clones including enterovirus A71 (EV-A71) and coxsackievirus B5 (CVB5). As described for EV-A71, the full-length cDNA of CVB5 was amplified by long-distance PCR and cloned into a T7 promoter-containing plasmid using directional seamless cloning technology. The virus was successfully rescued by single transfection into cells stably expressing T7 polymerase and exhibited characteristics similar to the parental virus. Next, through systematic construction and the optimization of the EV-A71 and CVB5 reporter viruses, we successfully generated two novel reporter virus panels with high virus titers, rapid replication, and relatively stable genetic inheritance across passages using the new fluorescence proteins mScarlet3-H and the smallest miRFP670nano3. Analysis of critical determinants for the reporter virus construction revealed that reporter gene sizes, genomic insertion sites, and the usage of protease recognition sites are crucial parameters. The EV-A71 and CVB5 reporter viruses enable antiviral drug evaluation, as demonstrated by our identification of gemcitabine as a broad-spectrum inhibitor of both viruses. These systems also facilitate the functional interrogation of host factors, exemplified by our discovery that METTL3 promotes EV-A71 and CVB5 replication. These reverse genetic tools, including infectious cDNA clones and reporter viruses, will advance basic enterovirus biology and accelerate antiviral drug discovery. Full article

Monkeypox virus (MPXV) is emerging as a global public health concern due to its nature of spread. There are limited treatment options, as the sole drug for treatment is lacking, highlighting the need for new therapeutic options. The use of computer-aided drugs discovery such as molecular docking, molecular dynamic (MD) simulations and post-simulation analysis are important tools in identifying potential compounds that can target specific proteins of the virus, such as DNA polymerase to stop virus replication. This study employed molecular docking and molecular simulation with the aim to identify potential inhibitors for MPXV treatment from the ZINC Database. Molecular docking was performed using PyRx 0.8 version after virtual screening of the ZINC database using the Tranches tool; then, toxicity prediction of the selected compounds was performed using the ProTox-3.0 web server. Molecular dynamics simulation was conducted using GROMACS version 4.5 to evaluate the structural stability and dynamic behavior of the protein–ligand complex for the best interacting compound. Furthermore, post-simulation analysis was conducted using standard GROMACS utilities for visualizing time-dependent properties from MD simulations. A total of 16 compounds were shortlisted based on their molecular docking scores and interaction profiles with the monkeypox virus DNA polymerase (PDB ID: 8HG1). The leading compound, ZINC000019418450, demonstrated strong binding affinity (−7.4 kcal/mol). According to post-simulation analysis, all top compounds formed between one and five hydrogen bonds and up to eleven hydrophobic contacts with residues within the active site, thus providing strong geometric and energetic evidence for binding stability. Notably, our identification of ZINC000104288636 as a Class 6 compound with an LD₅₀ of 23,000 mg/kg adds translational value by highlighting candidates with low predicted acute toxicity. Overall, this study lays a solid foundation for the rational design of next-generation monkeypox antiviral therapeutics. Future work is needed for experimental validation of prioritized compounds to assess their biochemical efficacy and pharmacological potential. Full article

Artificial intelligence (AI) is rapidly transforming virology by strengthening pandemic preparedness, enhancing our molecular understanding of virus–host interactions, and accelerating the discovery and development of novel antiviral therapies. Yet, the same technologies also pose urgent biosecurity risks, particularly by enabling the development of bioweapons or identifying strategies that maximize harm. This paper presents a critical content analysis of current and emerging AI applications in virology, including tools used to detect synthetic alterations in viral genomes, assess the severity of new variants, and design clinical vectors for gene therapy. It also highlights the potential for misuse, whether intentional or due to poor data quality and flawed model training. Drawing on case studies, public databases, and documented applications from research institutions and biotechnology firms, the analysis shows that AI can integrate large datasets to reduce reliance on animal testing in drug development, improve therapeutic precision, and allocate resources more effectively during outbreaks. However, the increasing accessibility of AI tools and genomic data also creates vulnerabilities, especially as models become capable of autonomously interpreting the scientific literature and mining bioinformatics databases. To address this dual-use dilemma, the paper proposes targeted and adaptable policy recommendations for governments, research institutions, and commercial biotech firms, emphasizing pre-emptive oversight, responsible innovation, and ethical AI deployment. These recommendations are designed for immediate relevance yet flexible enough to evolve alongside the expanding role of AI in global health. Full article

The MERS-CoV (Middle East respiratory syndrome coronavirus) is a zoonotic virus with a high mortality rate and a lack of antiviral drugs, underscoring the need for effective therapeutic methods. Viral entry depends on interactions between viral surface proteins and human receptors, with Dipeptidyl Peptidase-4 (DPP4), a transmembrane glycoprotein, acting as the receptor for MERS-CoV. We employed Molecular Dynamics (MD) Simulations to identify critical interface residues under a high-performance computing (HPC) workflow for accelerated results. Target residue pairs were identified through analysis of salt bridge and hydrogen bond occupancy. The stability of these residues was confirmed through three independent MD Simulations at human body temperature and constant pressure. Additionally, binding affinity predictions were calculated to determine the interaction strength between the virus and human receptors. Applying the scientific threshold criteria, we narrowed our results to seven key interaction pairs; two of the identified pairs (Asp510-Arg317, and Arg511-Asp393) are consistent with findings published in previous research studies, and five novel interactions are proposed for future experimental studies with our active collaborators in Pharmacology. The results provide a molecular basis for targeted mutation-based experiments and support the rational design of structure-based inhibitors aimed at disrupting the MERS-CoV-DPP4 complex, thereby facilitating the translation of computational findings into antiviral drug discovery. Full article

Monkeypox (Mpox), a zoonotic viral disease caused by the Monkeypox Virus (MPXV), has gained significant attention in recent years due to its increasing incidence and the grave threat it poses to global health. MPXV has spread at a rapid pace during the COVID-19 pandemic, causing 10,000+ confirmed cases and ~300 fatalities in 122 countries. This virus comprises two major clades, Clade I (Central African), which is evidently more virulent, and Clade II (West African), which has caused the recent outbreaks across the world and caused fewer deaths. Clinically, Mpox presents as a milder form with fever, lymphadenopathy, and vesiculopustular rash similar to smallpox. Diagnostic measures such as polymerase chain reaction (PCR) are the main diagnostic confirmatory tools. Advanced diagnostics involve electronic microscopy, serology, and immunohistochemistry. Alternative drugs like tecovirimat and brincidofovir have demonstrated potential for treating smallpox, but there is scanty evidence on their efficacy against MPXV. Most recent advancements in the study of vaccines have resulted in the creation and introduction of MVA-BN (JYNNEOS/Imvanex/Imvamune) and ACAM2000 vaccines, which conferred cross-protection against MPXV. MVA-BN is suggested to perform better than other types due to its enhanced safety and immunogenicity. Researchers are also developing DNA and protein subunit vaccines against Mpox to induce specific immune responses by presenting viral proteins. The discovery of novel vaccine candidates and antiviral treatments will be needed to prevent future outbreaks and reduce the global health burden of Mpox. This review focuses on the characterization of MPXV, summarizing current knowledge on its genomic structure, pathogenesis, replication, potential targets of anti-MPXV drugs, clinical features, and epidemiological patterns, along with recent advances in vaccine development. Full article

Gammaretroviruses are ubiquitous pathogens, often associated with the induction of neoplasia, especially leukemia, lymphoma, and sarcoma, and with a propensity to target the germline. The latter trait has left extensive evidence of their infectious competence in vertebrate genomes, the human genome being no exception. Despite the continuing activity of gammaretroviruses in mammals, including Old World monkeys, apes, and gibbons, humans have apparently evaded novel infections by the virus class for the past 30 million years or so. Nevertheless, from the 1970s onward, cell culture studies repeatedly discovered gammaretroviral components and/or virus replication in human samples. The last novel ‘human’ gammaretrovirus, identified in prostate cancer tissue, culminated in the XMRV frenzy of the 2000s. In the end, that discovery was shown to be due to lab contamination with a murine gammaretrovirus. Contamination is also the likely source of the earlier findings. Complementation between genes of partially defective endogenous proviruses could have been another source of the virions observed. However, the capacity of many gammaretroviruses to replicate in human cell lines, as well as the presence of diverse infectious gammaretroviral species in our animal companions, for instance in mice, cats, pigs, monkeys, chickens, and bats, does not make a transmission to humans an improbable scenario. This review will summarize evidence for, or the lack of, gammaretrovirus infections in humans in the past, present, and near future. Aspects linked to the probabilities of novel gammaretrovirus infections in humans, regarding exposure risk in connection to modern lifestyle, geography, diet, and habitat, together with genetic and immune factors, will also be part of the review, as will be the estimated consequences of such novel infections. Full article

Invertebrate iridescent viruses (IIVs, family Iridoviridae) are icosahedral double-stranded DNA viruses that infect a wide range of invertebrates, particularly in humid and aquatic environments. During field trials in Chiapas, southern Mexico, larvae of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), displayed an unexpected lavender iridescence, leading to the discovery of novel IIV isolates from this major agricultural pest. Restriction endonuclease analysis revealed evident diversity among isolates from individual infected larvae. Although one field experiment yielded inconclusive results, a second experiment revealed a positive association between IIV disease and SfMNPV infection, compared to a negative association with the prevalence of parasitoids, and no association with entomopathogenic nematodes (probably Hexamermis sp.). These findings require further investigation to determine the distinct ecological routes through which the virus may transmit across host species. IIV infection of S. frugiperda was also identified in Veracruz State, Mexico, and northern Argentina, revealing a previously unrecognized geographic and host range for these viruses. The genomic and evolutionary features of the three isolates from S. frugiperda were compared with those of two other lepidopteran isolates from Helicoverpa zea (IIV30C obtained from CSIRO) and Anticarsia gemmatalis (AgIIV). Genome sizes ranged between 196.1 and 205.4 kbp (~28% GC content), with several large inversions, and were rich in tandem repeats. The average amino acid identity of the complete genomes and phylogenetic analyses of 26 core gene sequences placed all five isolates within the genus Chloriridovirus, closely related to IIV22 and IV22a isolated from blackflies (Diptera) in Wales and a previously sequenced isolate of IIV30 from the USA. We conclude that these lepidopterans are all infected by closely related strains of the virus species Chloriridovirus simulium1 across their native geographical range. These findings highlight the unexpected ecological breadth and evolutionary adaptability of IIVs. Full article

Background/Objectives: Colombia harbors exceptional plant diversity, comprising over 31,000 formally identified species, of which approximately 6000 are classified as useful plants. Among these, 2567 species possess documented food and medicinal applications, with several traditionally utilized for managing febrile illnesses. Despite the global burden of dengue virus infection affecting millions annually, no specific antiviral therapy has been established. This study aimed to identify potential anti-dengue compounds from Colombian medicinal flora through machine learning-based quantitative structure–activity relationship (QSAR) modeling. Methods: An optimized XGBoost algorithm was developed through Bayesian hyperparameter optimization (Optuna, 50 trials) and trained on 2034 ChEMBL-derived activity records with experimentally validated anti-dengue activity (IC₅₀/EC₅₀). The model incorporated 887 molecular features comprising 43 physicochemical descriptors and 844 ECFP4 fingerprint bits selected via variance-based filtering. IC₅₀ and EC₅₀ endpoints were modeled independently based on their pharmacological distinction and negligible correlation (r = −0.04, p = 0.77). Through a systematic literature review, 2567 Colombian plant species from the Humboldt Institute’s official checklist were evaluated (2501 after removing duplicates and infraspecific taxa), identifying 358 with documented antiviral properties. Phytochemical analysis of 184 characterized species yielded 3267 unique compounds for virtual screening. A dual-endpoint classification strategy categorized compounds into nine activity classes based on combined potency thresholds (Low: pActivity ≤ 5.0, Medium: 5.0 < pActivity ≤ 6.0, High: pActivity > 6.0). Results: The optimized model achieved robust performance (Matthews correlation coefficient: 0.583; ROC-AUC: 0.896), validated through hold-out testing (MCC: 0.576) and Y-randomization (p < 0.01). Virtual screening identified 276 compounds (8.4%) with high predicted potency for both endpoints (“High-High”). Structural novelty analysis revealed that all 276 compounds exhibited Tanimoto similarity < 0.5 to the training set (median: 0.214), representing 145 unique Murcko scaffolds of which 144 (99.3%) were absent from the training data. Application of drug-likeness filtering (QED ≥ 0.5) and applicability domain assessment identified 15 priority candidates. In silico ADMET profiling revealed favorable pharmaceutical properties, with Incartine (pIC₅₀: 6.84, pEC₅₀: 6.13, QED: 0.83), Bilobalide (pIC₅₀: 6.78, pEC₅₀: 6.07, QED: 0.56), and Indican (pIC₅₀: 6.73, pEC₅₀: 6.11, QED: 0.51) exhibiting the highest predicted potencies. Conclusions: This systematic computational screening of Colombian medicinal flora demonstrates the untapped potential of regional biodiversity for anti-dengue drug discovery. The identified candidates, representing structurally novel chemotypes, are prioritized for experimental validation. Full article

Influenza A virus (IAV) poses a significant threat due to its rapid evolution through gene mutations and reassortments. Understanding host–virus protein interactions is vital for developing countermeasures. In this study, we developed a live-cell screening platform using the NanoBiT system for rapid discovery of host–virus protein–protein interactions (PPIs). Novel interactions between the host factor SNAPIN and the viral M1, M2 and NS2 were identified using this system. We confirmed the platform’s reliability by validating the SNAPIN-M1 interaction using independent methods including co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down assays. These results demonstrate the robustness of the PPI screening system and provide a basis for studying the role of SNAPIN in regulating IAV replication. Full article