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Prior Infection with Torque Teno Virus Mitigates Influenza Pathology in Mice
Effect of Acid-Stabilizing Hemagglutinin Mutations on Immunogenicity and Heterologous Protection by H1N1 Influenza Virus mRNA-LNP Vaccines
Dynamic Changes in Host Immune Response During Crimean–Congo Hemorrhagic Fever and Severe Fever with Thrombocytopenia Syndrome in Mice
Mapping Determinants of Hepatitis C Virus E1/E2 Transmembrane Interactions Using Intergenotypic Chimeras
RNA Folding Energy of Long-Range Genomic Interactions Regulates Discontinuous Transcription in SARS-CoV-2

Journal Description

Viruses

Viruses is a peer-reviewed, open access journal of virology, published monthly online by MDPI. The Spanish Society for Virology (SEV), Canadian Society for Virology (CSV), Italian Society for Virology (SIV-ISV), Australasian Virology Society (AVS), Brazilian Society for Virology (BSV) and Global Virus Network (GVN) are affiliated with Viruses and their members receive a discount on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, and other databases.
Journal Rank: JCR - Q2 (Virology) / CiteScore - Q1 (Infectious Diseases)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.5 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2026).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Journal Cluster of Microbiology: Acta Microbiologica Hellenica, Applied Microbiology, Bacteria, Journal of Fungi, Microorganisms, Microbiology Research, Pathogens, Viruses, Fermentation and Germs.

Impact Factor: 3.8 (2025); 5-Year Impact Factor: 3.8 (2025)

Imprint Information Journal Flyer Open Access ISSN: 1999-4915

Latest Articles

23 pages, 11888 KB

Open AccessArticle

Real-Time Imaging of HIV-1 Protease Activation and Substrate Cleavage in Single Virions Assembling on the Plasma Membrane

by Yinglin Li, Satya P. Singh, Mariana Marin, Alec L. Zhan, Ashwanth C. Francis and Gregory B. Melikyan

Viruses 2026, 18(8), 819; https://doi.org/10.3390/v18080819 (registering DOI) - 25 Jul 2026

The timing of HIV-1 protease (PR) activation and the determinants of orderly Gag and Gag-Pol polyprotein cleavage, leading to structural maturation of virions, are not well-understood. Here, we employed total internal reflection microscopy to visualize PR activation and cleavage of a FRET-based fluorescent [...] Read more.

The timing of HIV-1 protease (PR) activation and the determinants of orderly Gag and Gag-Pol polyprotein cleavage, leading to structural maturation of virions, are not well-understood. Here, we employed total internal reflection microscopy to visualize PR activation and cleavage of a FRET-based fluorescent substrate in single HIV-1 particles assembled on the cell’s ventral membrane. PR activity manifested as a reduction in FRET signal in a relatively small fraction of nascent viral particles. By contrast, most virions released from cells contained a processed FRET substrate, suggesting that PR activation may be delayed or suppressed in most virions assembled at the ventral membrane. A combination of single-particle tracking and FRET measurements detected PR activity, on average, within ~20 min after the onset of particle assembly, while cleavage of a FRET substrate in single virions was completed within a few minutes. Importantly, substrates containing distinct PR cleavage sequences derived from Gag and Gag-Pol polyproteins were processed with different rates and efficiency. Our findings validate the use of surrogate FRET substrates to assess the timing of PR activation in single virions and elucidate the determinants of the tightly orchestrated order of Gag and Gag-Pol cleavage required for the formation of infectious virions. Full article

(This article belongs to the Special Issue Microscopy Methods for Virus Research, 2nd Edition)

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16 pages, 2040 KB

Open AccessArticle

Development of a Novel Immune Gene Array to Assess Mosquito Gene Expression During Arbovirus Infection

by Juliette Lewis, Dahlia Kopycienski, Dana Mitzel and Rebekah C. Kading

Viruses 2026, 18(8), 818; https://doi.org/10.3390/v18080818 (registering DOI) - 25 Jul 2026

Assessing mosquito vector competence for emerging arboviruses, including the underlying determinants of infection, is a foundational line of investigation towards understanding arbovirus transmission dynamics and vector–virus interactions. We developed a novel quantitative immune gene array that measures the relative expression of 22 immune [...] Read more.

Assessing mosquito vector competence for emerging arboviruses, including the underlying determinants of infection, is a foundational line of investigation towards understanding arbovirus transmission dynamics and vector–virus interactions. We developed a novel quantitative immune gene array that measures the relative expression of 22 immune genes with functional representation across five major immune pathways using quantitative reverse-transcriptase polymerase chain reaction. Homologous primers were developed for Culex tarsalis, Cx. quinquefasciatus, and Ae. aegypti mosquitoes. As an initial pilot test for this array, Cx. tarsalis and Ae. aegypti mosquitoes were orally challenged with Rift Valley fever virus (RVFV) MP12 strain. Midguts, legs/wings, and salivary glands were harvested at 3 and 7 days post-challenge. Differential gene expression was measured against Rpl32 as a housekeeping gene. This assay was sensitive enough to generate results for single mosquito midgut and salivary gland tissues, providing an initial snapshot of the types of gene expression patterns that can be observed for two mosquito species infected with MP12. This new tool will be broadly applicable for assessing mosquito immune profiles for arbovirus infection across major immune genes in five key pathways, as well as generating comparable results across mosquito and arbovirus systems. Full article

(This article belongs to the Collection Emerging Arboviruses, Volume II)

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19 pages, 1237 KB

Open AccessArticle

Cat-Related Injuries and Rabies Exposure: A Three-Decade Retrospective Analysis from the Zagreb Antirabies Clinic (1995–2025)

by Krešimir Tućin, Dora Primorac, Ivana Lojkić and Radovan Vodopija

Viruses 2026, 18(8), 817; https://doi.org/10.3390/v18080817 (registering DOI) - 25 Jul 2026

Cat-related injuries are a frequent reason for antirabies consultation, but long-term data on their epidemiology and management remain limited, particularly in European settings that have transitioned from endemic sylvatic rabies to officially rabies-free status. We retrospectively analysed registry data on all patients examined [...] Read more.

Cat-related injuries are a frequent reason for antirabies consultation, but long-term data on their epidemiology and management remain limited, particularly in European settings that have transitioned from endemic sylvatic rabies to officially rabies-free status. We retrospectively analysed registry data on all patients examined for cat-related injuries at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies, between 1995 and 2025. Among 24,107 animal-related consultations, 3147 (13.1%) involved cats. Most patients were female (64.8%), and children under 18 years of age accounted for 14.7% of the patients. The offending cat had a known owner in 48.5% of cases and was unknown in 45.9%. Records associated with laboratory-confirmed rabid cats accounted for 4.8%, all from 1995 to 2012. Post-exposure prophylaxis (PEP) was administered to 37.6% of patients, and human rabies immunoglobulin (HRIG) to 2.9%. Hospitalisation was rare (1.1%), while injuries most often involved the fist and fingers (59.5%). PEP administration was strongly associated with the rabies risk status of the offending cat, increasing from 8.7% for known-owner cats to 62.0% for unknown cats and approximately 87% for suspected or laboratory-confirmed rabid cats (p < 0.001). In multivariable analysis, animal status remained the principal factor independently associated with PEP (adjusted odds ratio for unknown versus known-owner cats approximately 18), whereas patient characteristics had limited effect. HRIG use declined below 1% in 2015–2025, paralleling the elimination of sylvatic rabies in Croatia. Continued structured exposure assessment remains relevant despite rabies-free status, particularly when cats are unknown or unavailable for observation. Full article

(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention—2nd Edition)

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17 pages, 327 KB

Open AccessReview

Measles: A Narrative Review of Current Therapeutic Options and Implications for the Future

by Amalia Papanikolopoulou, Ilektra Tseliou and Helena C. Maltezou

Viruses 2026, 18(8), 816; https://doi.org/10.3390/v18080816 (registering DOI) - 25 Jul 2026

Despite the availability of a safe and effective measles vaccine for several decades, measles remains a significant cause of morbidity and mortality worldwide, causing 95,000 deaths in 2024 alone. Currently, there is no licensed therapeutic agent against measles, and treatment is only supportive. [...] Read more.

Despite the availability of a safe and effective measles vaccine for several decades, measles remains a significant cause of morbidity and mortality worldwide, causing 95,000 deaths in 2024 alone. Currently, there is no licensed therapeutic agent against measles, and treatment is only supportive. This is a review of articles published from 2015 to 3 June 2025, on therapeutic agents used or under investigation against measles. Ribavirin has been used in severe measles cases; nevertheless, there are no randomized clinical trials so far. New delivery systems, such as polymer-based formulations and nanoparticles, have markedly increased ribavirin’s efficacy, while cytotoxicity remained low. Viral membrane fusion (F) protein inhibitors and viral RNA polymerase inhibitors are promising next-generation therapeutics against measles and have been tested in animal models with good results. Lastly, interferons (IFNs) are key mediators of the innate immune response against measles, particularly for controlling brain infection. There are few reports indicating that repeated remdesivir courses, as well as intraventricular or intrathecal ribavirin or IFN, may temporarily stabilize the neurologic status of patients with subacute sclerosing panencephalitis. Intracranial administration of protein F inhibitors also demonstrated promising results in mice. Although several antiviral agents and natural products exhibit in vitro efficacy against measles virus, further research is required to determine their safety, pharmacological properties, and clinical efficacy before they can be considered therapeutic options. Overall, the development of antiviral agents against measles has been extremely slow. Therapeutic agents against measles are urgently needed. Full article

(This article belongs to the Special Issue Advances in Measles Virus Research, Vaccine Development and Vaccination Strategies)

24 pages, 9595 KB

Open AccessArticle

Human Coronavirus Photodynamic Inactivation and In Silico Mechanisms Induced by Ga(III) vs. Zn(II) Phthalocyanines

by Neli Vilhelmova-Ilieva, Emilio Mateev, Muhammed Tilahun Muhammed, Aleksandra Rangelova, Diana Braikova, Ivan Iliev and Vanya Mantareva

Viruses 2026, 18(8), 815; https://doi.org/10.3390/v18080815 - 24 Jul 2026

Photodynamic inactivation (PDI) is a relatively new approach for targeting viruses. Recently, PDI has been shown to be effective against various viral infections, with a low probability of resistance development. The study presents PDI towards the infectivity of human coronavirus (HCoV-OC43) at different [...] Read more.

Photodynamic inactivation (PDI) is a relatively new approach for targeting viruses. Recently, PDI has been shown to be effective against various viral infections, with a low probability of resistance development. The study presents PDI towards the infectivity of human coronavirus (HCoV-OC43) at different stages of its propagation and through different mechanisms of action. Two tetra-methylpyridiloxy-substituted gallium and zinc phthalocyanines (GaPcMe and ZnPcMe), exposed to light from a 660 nm light-emitting diode (LED), were evaluated and showed a high potential against HcoV-OC43. The effect of PDI on extracellular virions and the stage of their adsorption was assessed using the finite dilution method and by determining changes in viral infectivity (Δlgs). The impact on the viral replicative cycle was assessed by inhibition of the cytopathic effect (CPE). The direct effect on virions was notable for both phthalocyanines, but was significantly more pronounced for ZnPcMe (Δlg = 4). A strong inhibitory effect on virus adsorption was observed for ZnPcMe (from Δlg = 3.5 to complete inhibition, Δlg = 5.0, depending on the irradiation time). Both GaPcMe and ZnPcMe demonstrate PDI at an early stage of the virus replication cycle. This is reflected in the high photoinactivation indices PII = 44.0 for ZnPcMe and PII = 23.3 for GaPcMe. The binding potential of GaPcMe and ZnPcMe toward viral and host protein targets was investigated using molecular docking and molecular dynamics (MD) simulations. The computational panel included HCoV-OC43 3CLpro (Nsp5, PDB 9PAM) and homologous SARS-CoV-2 proteins, namely Nsp5, Nsp12, M protein, S protein, as well as human ACE2. The docking results indicated that both phthalocyanines exhibit notable theoretical binding affinity toward these targets. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))

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21 pages, 1175 KB

Open AccessArticle

Evolutionarily Optimal Phage Life-History Traits: Burst Size vs. Lysis Time

by Joan Roughgarden

Viruses 2026, 18(8), 814; https://doi.org/10.3390/v18080814 - 24 Jul 2026

A model based on a dynamical equation for the virus-to-microbe ratio (VMR) during log phase population growth shows that an optimal balance occurs between a short lysis time with low burst size vs. a long lysis time with large burst size. The model [...] Read more.

A model based on a dynamical equation for the virus-to-microbe ratio (VMR) during log phase population growth shows that an optimal balance occurs between a short lysis time with low burst size vs. a long lysis time with large burst size. The model predicts that interventions lowering phage adsorption by killing free virus and/or limiting their access to bacteria favors the evolution of an increased lysis time and higher burst per infecting microbe until the intervention either drives a virulent phage extinct or, for temperate phage, drives the phage from its lytic phase into its lysogenic phase. The model also predicts that along an environmental gradient of increasing primary productivity the optimal lysis time shortens along the gradient, implying that the lytic life cycle goes around faster along the gradient. Full article

(This article belongs to the Special Issue Phage Evolution: Taxonomy, Origins, and Diversity)

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20 pages, 7625 KB

Open AccessReview

Immunometabolism in HIV Reservoirs: Implications for Latency and Comorbidities

by Mary-Elizabeth Zipparo and Rebecca T. Veenhuis

Viruses 2026, 18(8), 813; https://doi.org/10.3390/v18080813 - 24 Jul 2026

Compelling research has consistently demonstrated a strong relationship between immunometabolism and infectious disease, including the ways in which viral infections alter the metabolic state of immune cells to promote survival. Human immunodeficiency virus (HIV) has been particularly noted for its ability to reprogram [...] Read more.

Compelling research has consistently demonstrated a strong relationship between immunometabolism and infectious disease, including the ways in which viral infections alter the metabolic state of immune cells to promote survival. Human immunodeficiency virus (HIV) has been particularly noted for its ability to reprogram the metabolism of cells that contribute to viral persistence. The purpose of this review is to summarize current knowledge of the metabolic state of CD4 T cells and myeloid cells (monocytes/macrophages), two of the primary cell types targeted by HIV. The studies discussed reveal distinct metabolic profiles in both cell types during initial infection, active replication, and latency. In addition, we examine how these metabolic alterations may contribute to the increased frequency and severity of comorbidities observed in people with HIV (PWH). Understanding the impact of HIV infection and latency on immunometabolism may provide deeper insight into long-term viral persistence and support the identification of novel therapeutic targets to reduce chronic inflammation and inform future cure strategies for PWH. Full article

(This article belongs to the Special Issue HIV-1 Infection and Immunometabolism: Relevance to HIV Pathogenesis and Persistence 3.0)

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26 pages, 1678 KB

Open AccessReview

Non-Sexual Transmission of Papillomavirus: Is It Part of Our Virome?

by Sandro La Vignera and Rosita A. Condorelli

Viruses 2026, 18(8), 812; https://doi.org/10.3390/v18080812 - 24 Jul 2026

Background: Human papillomavirus (HPV) has traditionally been considered a sexually transmitted infection, yet accumulating evidence demonstrates that HPV can be acquired through multiple non-sexual routes. Understanding these alternative transmission pathways is critical for interpreting HPV detection in non-sexually active populations and for refining [...] Read more.

Background: Human papillomavirus (HPV) has traditionally been considered a sexually transmitted infection, yet accumulating evidence demonstrates that HPV can be acquired through multiple non-sexual routes. Understanding these alternative transmission pathways is critical for interpreting HPV detection in non-sexually active populations and for refining public health strategies. Methods: This review synthesizes current evidence on non-sexual HPV transmission routes, including vertical (transplacental, intrapartum), perinatal oropharyngeal colonization, fomite contamination, breast milk transmission, and horizontal non-sexual contact. We examine HPV prevalence data from female virgins, neonates, infants, and children, and evaluate metagenomic evidence positioning HPV as a component of the human virome across multiple body sites. Results: Published studies report that vertical transmission occurs in approximately 18.2% of HPV-positive mothers, with neonatal HPV positivity of 3.4% at birth and 100% genotype concordance in transmission pairs. Transplacental transmission has been documented in 10.2% of concordant mother–placenta–newborn triads. Reviewed studies report oropharyngeal colonization at birth reaching 58.2% following vaginal delivery, with 94.3% of colonized neonates clearing infection by 24 months. HPV DNA has been detected on fomites and medical devices, in breast milk (8.6–15%), and across body sites in healthy adults (skin 61.3%, vagina 41.5%, oral cavity 30%, gut 17.3%). Metagenomic studies identify HPV DNA in 68.9% of healthy individuals, with 109 distinct types detected. Female virgins show HPV prevalence ranging from 0–51.1% across studies. Conclusions: The reviewed evidence suggests that HPV exhibits characteristics of a ubiquitous virome component with multiple non-sexual acquisition routes. These findings have important implications for vaccination strategies, screening interpretation, infection control in healthcare settings, and counseling of pediatric cases and non-sexually active individuals. Full article

(This article belongs to the Special Issue The Life Cycle of Human Papillomaviruses)

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18 pages, 1298 KB

Open AccessReview

HIV-1 Env Heterogeneity: Cleavage, Trafficking, and Antigenic Consequences for Virions and Infected Cells

by Dania M. Figueroa Acosta, Sara Khaleeq, Svenja Weiss, Tony R. Valencia, Guy Mason and Benjamin K. Chen

Viruses 2026, 18(8), 811; https://doi.org/10.3390/v18080811 - 24 Jul 2026

The HIV-1 Env glycoprotein mediates both cell-free and cell-to-cell viral transmission and represents the primary target for protective humoral immune responses. Studies examining antibody neutralization of cell-free and cell-to-cell HIV transmission have found that cell-to-cell transmission is more resistant to neutralization. This resistance [...] Read more.

The HIV-1 Env glycoprotein mediates both cell-free and cell-to-cell viral transmission and represents the primary target for protective humoral immune responses. Studies examining antibody neutralization of cell-free and cell-to-cell HIV transmission have found that cell-to-cell transmission is more resistant to neutralization. This resistance may be explained in part by antigenically distinct Env populations on virions and infected cells. Cell-surface Env may be more heterogeneous due to variations in cleavage, glycosylation, and conformational state. Nevertheless, the mechanisms that maintain antigenically distinct Env populations at the cell surface and on virions remain unclear, despite virion assembly occurring at the plasma membrane. In this focused review, we consider how Env endocytosis and recycling influence Env incorporation into virions and antibody recognition. We further consider how Env cleavage may influence trafficking and endocytic fate. Given the central role of Env’s cytoplasmic tail in engaging endosomal trafficking pathways, we review emerging structural models of the CT and discuss how its organization, symmetry, and conformational flexibility may contribute to Env trafficking and intracellular sorting. We also discuss how heterogeneous Env populations may influence antibody susceptibility. Finally, we review therapeutic strategies, including combinatorial antibodies and small-molecule Env modulators, that may enhance antibody recognition of infected cells and virions. Full article

(This article belongs to the Special Issue Molecular Insights into HIV-1 Infection)

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21 pages, 7207 KB

Open AccessArticle

Cross-Species Spillover of Tiger Frog Virus Caused Lethal Systemic Disease in Captive Geochelone sulcata: Etiology, Pathology, and Genomic Characterization

by Chuchu Lai, Fen Shan, Danning Song, Minxin Chen, Minghui He, Zujin Chen and Xuezhu Lee

Viruses 2026, 18(8), 810; https://doi.org/10.3390/v18080810 - 23 Jul 2026

In 2025, a severe mass mortality outbreak struck captive Geochelone sulcata at a zoo in Guangdong Province, China. To trace the causative agent, identify the viral strain and characterize associated pathological lesions, respiratory tract samples collected from diseased tortoises were subjected to a [...] Read more.

In 2025, a severe mass mortality outbreak struck captive Geochelone sulcata at a zoo in Guangdong Province, China. To trace the causative agent, identify the viral strain and characterize associated pathological lesions, respiratory tract samples collected from diseased tortoises were subjected to a combined technical workflow. Metagenomic high-throughput sequencing was first applied to screen for potential pathogens, followed by virus isolation via cell culture. Transmission electron microscopy (TEM) was used to observe viral morphology. The major capsid protein (MCP) gene was amplified by PCR for molecular identification, and whole-genome sequencing together with phylogenetic analysis was performed to clarify the genetic features of the isolate. The results verified that ranavirus was the primary pathogen responsible for the mortality. Pathological examination demonstrated acute necrosis, hemorrhage and inflammatory infiltration in multiple organs including the liver, spleen, lung, and pancreas. TEM observation revealed typical iridovirus-like particles with an average diameter of approximately 70 nm. Molecular and genomic analyses confirmed the pathogen as Tiger Frog Virus (TFV) of the genus Ranavirus, designated TFV-CN2025, which shared 99.8% nucleotide sequence homology with known TFV reference strains. To our knowledge, this is the first report of lethal TFV infection in G. sulcata, which provides detailed pathological evidence for this cross-species transmission event from amphibian hosts to terrestrial chelonians. Our findings indicate that TFV poses considerable risks to the tortoise breeding industry and ecological security in China. We therefore suggest incorporating TFV detection into routine quarantine and disease surveillance programs for captive tortoises. Full article

(This article belongs to the Special Issue Viral Diseases of Aquatic Animals: Crustaceans, Mollusks, Fish, Sea Turtles, and Marine Mammals)

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23 pages, 12744 KB

Open AccessArticle

Target-Oriented Screening of Traditional Chinese Medicine Potential Inhibitors Against African Swine Fever Virus dUTPase and Preliminary Evaluation of Enzymatic Activity Effects

by Mengqi Zhao, Xinyu Dai, Hao Tang, Changde Wu, Junjuan Fan, Shouhua Feng, Kang Ou, Gen Lu, Xuesong Fang, Xiaoyue Chen, Shu Wei, Zuofeng Yang and Jinling Liu

Viruses 2026, 18(8), 809; https://doi.org/10.3390/v18080809 - 23 Jul 2026

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease that has brought severe economic losses to the global swine industry. ASFV dUTPase is a key enzyme modulating viral nucleotide metabolism and genome stability, serving as a [...] Read more.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease that has brought severe economic losses to the global swine industry. ASFV dUTPase is a key enzyme modulating viral nucleotide metabolism and genome stability, serving as a specific structural target for anti-ASF lead discovery. Based on the crystal structure of ASFV dUTPase (Georgia 2008/1 strain), we established a molecular docking model to virtually screen a Traditional Chinese Medicine (TCM) compound library following ADME-based filtration. We further conducted 100 ns molecular dynamics (MD) simulations via GROMACS and calculated binding free energies using the MM/PBSA method, followed by in vitro enzymatic inhibition assays for verification. Four candidate compounds, namely Salvianolic acid B, Kukoamine B, Ligustroflavone and 9‴-Methyl salvianolic acid B, showed favorable structural accommodation and binding potential. In vitro tests indicated that Ligustroflavone and 9‴-Methyl salvianolic acid B exhibited preliminary inhibitory activity against ASFV dUTPase, with IC₅₀ values of 1.87 mM and 0.92 mM, respectively, while Kukoamine B showed no inhibitory effect. This study identified potential TCM-derived lead molecules targeting ASFV dUTPase, providing new references and candidate compounds for the development of anti-ASF therapeutics. Full article

(This article belongs to the Collection African Swine Fever Virus (ASFV))

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9 pages, 189 KB

Open AccessEditorial

Mpox Beyond Emergence: Scientific Advances, Persistent Inequities, and Future Directions

by Patrick M. Katoto, Robert Colebunders and David A. Schwartz

Viruses 2026, 18(8), 808; https://doi.org/10.3390/v18080808 - 23 Jul 2026

The global epidemiology of mpox has undergone a profound transformation over the past decade, evolving from a historically neglected zoonotic infection into a complex and expanding international public health challenge [...] Full article

(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)

18 pages, 1277 KB

Open AccessArticle

Genotypes of Bovine Viral Diarrhea Virus Infecting Vaccinated and Nonvaccinated Cattle in Thrace District, Türkiye

by Gizem Karadag, Hasan Emre Tali, Ismail Egemen Ozkan, Nuri Turan, Sajid Umar, Juergen A. Richt, Huseyin Yilmaz and Aysun Yilmaz

Viruses 2026, 18(8), 807; https://doi.org/10.3390/v18080807 - 23 Jul 2026

Bovine viral diarrhea virus (BVDV) is a major cause of economic losses in the global cattle industry. This study investigated the clinical involvement and genetic diversity of BVDV in clinically affected cattle from the Thrace region in Türkiye, a critical border area with [...] Read more.

Bovine viral diarrhea virus (BVDV) is a major cause of economic losses in the global cattle industry. This study investigated the clinical involvement and genetic diversity of BVDV in clinically affected cattle from the Thrace region in Türkiye, a critical border area with the European Union. A total of 533 nasal and rectal swabs were collected from 26 farms exhibiting clinical respiratory disease or diarrhea and analyzed using real-time RT-PCR. Positive samples were further characterized by sequencing and phylogenetic analysis to determine viral genotypes and subgenotypes. BVDV RNA was detected in 9 out of 26 farms (34.6%), with an overall positivity rate of 17.8% (95/533). Statistical analysis revealed significant associations between PCR positivity and both sampling year (p < 0.05) and animal age (p < 0.05). Genetic analysis of partial 5′-UTR sequences identified nine Pestivirus bovis subgenotype 1a strains, one Pestivirus bovis subgenotype 1f, and one Pestivirus brazilense. The Pestivirus bovis 1a strains clustered distinctly from previously reported Turkish BVDV-1 isolates, showing 97.32–99.11% nucleotide similarity with strains from Türkiye, Germany, China, Japan, the USA, Iran, and Argentina. Among the 533 samples tested, one Pestivirus brazilense isolate was identified, indicating its rare occurrence in the studied population despite targeted screening. This study represents the first report of Pestivirus brazilense in the Thrace region of Türkiye, expanding its known geographic range. The epidemiological data and genetic diversity analysis of BVDV strains characterized in this study offer critical insights for refining BVDV control programs, informing regional risk assessment, and supporting vaccine development. Full article

(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)

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38 pages, 3811 KB

Open AccessReview

Chalcones as a Versatile Antiviral Scaffold: Molecular Targets, ADMET Profiles, and Translational Challenges

by Alvaro Luiz Helena, Patrick Rômbola Ozanique, Kevin Henrique Souza Lima, Wellington Negri Tondato, Victor Yukio Ichikawa Baio, Otávio Henrique Locateli Soares and Luis Octávio Regasini

Viruses 2026, 18(7), 806; https://doi.org/10.3390/v18070806 - 22 Jul 2026

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 [...] Read more.

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

(This article belongs to the Special Issue Natural, Semisynthetic, and Synthetic Antiviral Drugs: Combating Emerging and Re-Emerging Viral Threats)

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22 pages, 1338 KB

Open AccessArticle

Association of ABO/Rh Blood Groups and ABO Gene Variants rs8176746 and rs495828 with COVID-19 Severity Among Egyptian Patients

by Marwa H. Elnagdy, Alshimaa Magdy, Ahmed Hazem El-Nagdy, Eman Ali Elkordy, Ahmed E. Taha, Atef Elmougy, Mohamed Ayed Rashwan, Basil Mohammed Alomair, Anas Adi, Waleed Eldars, Mohamed Elgamal, Mohamed Ahmed Noureldin, Mayada Sabry Zeid and Ali Sobh

Viruses 2026, 18(7), 805; https://doi.org/10.3390/v18070805 - 22 Jul 2026

The link between ABO/Rh blood groups and COVID-19 severity remains a topic of debate. We aimed to investigate the role ABO/Rh blood groups, rs8176746 and rs495828 single nucleotide polymorphisms (SNPs), in COVID-19 severity among COVID-19 patients in Mansoura City, Egypt. A total of [...] Read more.

The link between ABO/Rh blood groups and COVID-19 severity remains a topic of debate. We aimed to investigate the role ABO/Rh blood groups, rs8176746 and rs495828 single nucleotide polymorphisms (SNPs), in COVID-19 severity among COVID-19 patients in Mansoura City, Egypt. A total of 306 Egyptian patients were included in this cross-sectional study. They were grouped into 86 cases with non-severe infection and 220 with severe infection according to clinical, laboratory, and radiological findings. ABO/Rh blood groups were confirmed. A TaqMan real-time PCR SNP genotyping assay was used to examine the allelic discrimination of rs8176746 and rs495828 SNPs. Older age, male gender, and the presence of comorbidities were associated with severe COVID-19. AB blood group was significantly associated with a protective effect against severe COVID-19 (p = 0.029) in the unadjusted analysis. There was no statistically significant association between Rh type and disease severity. GT genotype was significantly associated with a higher frequency of AB blood groups in both rs8176746 and rs495828 (p < 0.001). However, there was no statistically significant association between the studied SNPs and COVID-19 severity. After adjusting for age, gender, and the presence of comorbidities, the protective effect of the AB blood group with severe COVID-19 did not remain significant. No association was observed between Rh type rs8176746 and rs495828 SNPs and COVID-19 severity. The impact of ABO/Rh blood types and related SNPs on COVID-19 severity can vary by the ethnic group and population being studied. This diversity emphasizes the need for specialized research approaches to better understand the demographic, clinical, and genetic factors that lead to variations in COVID-19 outcomes among various groups. Full article

(This article belongs to the Section Coronaviruses)

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35 pages, 3238 KB

Open AccessReview

Drug Repurposing as a Broad-Spectrum Strategy Against Coronaviruses: Frontiers in Mechanisms and Clinical Translation

by Shuai Du, Yue Wang, Chao Liu, Yiming Han, Rui Zong, Shen Wang, Wenjuan Du, Linyang Yu and Yongtao Li

Viruses 2026, 18(7), 804; https://doi.org/10.3390/v18070804 - 21 Jul 2026

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant [...] Read more.

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant challenges to global health. In this context, drug repurposing has emerged as a practical strategy for rapidly identifying broad-spectrum antivirals against emerging and re-emerging coronaviruses. Using coronaviruses as a paradigm, this review systematically summarizes research advances and mechanistic insights into the repurposing of existing drugs against coronaviruses. Simultaneously, we dissect core challenges including species-specific pharmacokinetic disparities, insufficient inter-genera conservation of viral targets, and systemic barriers between human and veterinary drug regulatory frameworks and propose innovative solutions encompassing AI-driven cross-species drug prediction, next-generation cross-species infection models, and a “human-veterinary dual-track” collaborative research and development system. Collectively, this review highlights the promise of drug repurposing as a broad-spectrum antiviral strategy and provides a translational perspective for the development of cross-species anti-coronavirus therapeutics. Full article

(This article belongs to the Special Issue Broad-Spectrum Antiviral Strategies Against Emerging and Re-Emerging Viral Diseases)

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33 pages, 21367 KB

Open AccessArticle

Structural Prediction and Antigenic Characterization of Recombinant Nucleocapsid Protein (p14) of Small Ruminant Lentivirus

by María Azucena Castañeda-Montes, José Luis Cerriteño-Sánchez, Julieta Sandra Cuevas-Romero, Francisco Jesus Castañeda-Montes, Dalia González-Esparragoza, Lucero de María Ávila-De la Vega and Hugo Ramírez-Álvarez

Viruses 2026, 18(7), 803; https://doi.org/10.3390/v18070803 - 21 Jul 2026

Small ruminant lentivirus (SRLV) infects goats and sheep of all breeds and ages worldwide. There are no current records regarding the three-dimensional structure or antigenic capacity of the nucleocapsid protein p14 of FESC-752 Mexican strain. The antigenic structure of p14 protein of a [...] Read more.

Small ruminant lentivirus (SRLV) infects goats and sheep of all breeds and ages worldwide. There are no current records regarding the three-dimensional structure or antigenic capacity of the nucleocapsid protein p14 of FESC-752 Mexican strain. The antigenic structure of p14 protein of a B1 genotype was predicted. cDNA from FESC-752 was used to overexpress the recombinant SRLV-rp14 protein. Then, its antigenicity was verified in vitro by evaluating plasma samples from goats and sheep naturally infected with SRLV. Antigenicity prediction showed a “horseshoe”-type structure shared by different lentiviruses and five epitopes distributed throughout the p14 surface regions where they coincide suggesting conserved epitopes in the zinc-finger structures of the nucleoproteins of the SRLV, Human Immunodeficiency Virus (HIV-1), and Feline Immunodeficiency virus (FIV) retroviruses. Multi-species molecular docking showed a notable structural convergence where caprine, bovine, murine, and human immunoglobulins target a predictive 23 amino acid epitope (residues 41–64) within the core zinc-finger region. Furthermore, CABS docking simulations predicted that p14-derived peptides preferentially bind within the antigen-presenting cleft of both caprine and bovine major histocompatibility complex class I (MHC-I) molecules. The stability of these immunological complexes is mediated by dense networks of hydrophobic interactions and highly conserved aromatic anchoring residues. Antigenicity analysis revealed that 78.7% of samples from naturally infected goats showed immunoreactivity toward SRLV-rp14 and the predictive evidence that p14 can simultaneously stimulate both humoral and cellular pathways makes it a strategic candidate for the design of next-generation vaccines aimed at controlling lentiviruses in small ruminants. Full article

(This article belongs to the Special Issue Viral Diseases of Sheep and Goats)

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16 pages, 8607 KB

Open AccessArticle

Toxic Relationships: Characterization of a Putative Virally Encoded Toxin in the Thermophilic Archaeal Fusellovirus SSV1

by Jonathan C. Abshier, Patrizia L. Alpapara, Guasåli Tomokane and Kenneth M. Stedman

Viruses 2026, 18(7), 802; https://doi.org/10.3390/v18070802 - 21 Jul 2026

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and [...] Read more.

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and virion production. Viruses lacking ORF a291 replicated their genomes and formed morphologically normal spindle-shaped particles, yet failed to inhibit the growth of uninfected Saccharolobus solfataricus. Substitution of residues at a predicted N-terminal signal peptide cleavage site abolished growth suppression without affecting replication, suggesting that secretion is essential for toxin function. Despite primary sequence divergence among fusellovirus toxin candidates, analysis of protein structure predictions revealed a conserved hydrolase-like fold across SSV1, SSV9 and SSV10 toxins. These findings demonstrate functional separation of viral replication and host growth suppression and support a model in which chronic archaeal viruses modulate host competition through antagonistic factors. This work expands the known diversity of putative viral toxins and suggests that fuselloviruses employ conserved strategies to promote persistence in extreme environments. Full article

(This article belongs to the Special Issue Viruses in Extreme Environments)

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23 pages, 9384 KB

Open AccessArticle

A Viral Long Non-Coding RNA Modulates Viral RNA Silencing Suppressor and DCL4-Associated DRB4 Protein Interaction

by Amélie Janzam, Lucie Bellott, Johana Chicher, Philippe Hammann, Camille Kempff, Line Jambois, Kamal Hleibieh, Fabrice Michel, Véronique Ziegler-Graff and David Gilmer

Viruses 2026, 18(7), 801; https://doi.org/10.3390/v18070801 - 20 Jul 2026

The expression of the BNYVV silencing suppressor (VSR) p14 protein, together with the production of a viral non-coding RNA (ncRNA3), affects the long-distance movement on natural host Beta species. Through immunoprecipitation of Flag-p14 and expression of TurboID-p14 coupled to mass spectrometry, we identified [...] Read more.

The expression of the BNYVV silencing suppressor (VSR) p14 protein, together with the production of a viral non-coding RNA (ncRNA3), affects the long-distance movement on natural host Beta species. Through immunoprecipitation of Flag-p14 and expression of TurboID-p14 coupled to mass spectrometry, we identified several potential p14 cellular partners. These include proteins related to RNA metabolism, proteasome activation, and notably, SGS3—a key player in the siRNA transitivity pathway—and DRB4, the DCL4 cofactor described in A. thaliana silencing pathways. The interaction between p14 and DRB4 was specifically retrieved with the hypomorphic p14BA2 VSR mutant in nucleoli and was disrupted in the presence of ncRNA3, a condition that allows the viral mutant to move long distances. Subcellular fractionation of infected tissues revealed that ncRNA3 accumulates in the nucleus through its interaction with p14, while genomic RNA3 remains cytoplasmic. Our results suggest that a specific viral RNA is targeted to the nucleus to participate in silencing suppression function by destabilizing the p14-DRB4 complex. Moreover, the interaction between p14 and SGS3 provides a mechanistic explanation of the role of this VSR in silencing transitivity. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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29 pages, 2822 KB

Open AccessReview

Opportunistic CNS Viral Infections in Immunocompromised Patients

by Adriana A. M. Giuliani and Nancy Law

Viruses 2026, 18(7), 800; https://doi.org/10.3390/v18070800 - 20 Jul 2026

Immunocompromised patients face increased morbidity and mortality from central nervous system (CNS) opportunistic viral infections, with risk level driven by specific immune defects. While our diagnostic capacity expands, immunocompromised patients may present atypically or with mild symptoms, delaying or complicating diagnosis. Treatment options [...] Read more.

Immunocompromised patients face increased morbidity and mortality from central nervous system (CNS) opportunistic viral infections, with risk level driven by specific immune defects. While our diagnostic capacity expands, immunocompromised patients may present atypically or with mild symptoms, delaying or complicating diagnosis. Treatment options are often limited, although novel agents show promise. This review discusses why immunocompromised patients carry higher immunologic risk and how certain viral classes display neurotropism to invade the CNS. We outline the utility and limitations of current and emerging diagnostic strategies. We discuss specific opportunistic viral pathogens, denoting specific epidemiology or pathogenesis, clinical presentation, diagnostic findings, and treatment and prevention methods. While there still remain knowledge and treatment gaps, advancements in diagnostics and understanding of pathogens have begun to improve outcomes. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections, 3rd Edition)

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