Search Results (219)

Corneal endotheliitis is an inflammatory process, most commonly of viral etiology, that manifests clinically with features including corneal edema, keratic precipitates, and a mild anterior chamber reaction. Several studies have implicated human herpesviruses from the Herpesviridae family as primary causes of corneal endotheliitis, including cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex viruses 1 and 2 (HSV-1 and HSV-2). This review critically evaluates the present literature surrounding herpesvirus infections of the corneal endothelium. Full article

The COVID-19 pandemic, driven by the high transmissibility and immune evasion caused by SARS-CoV-2 and its variants (e.g., Alpha, Delta, Omicron), has led to massive casualties worldwide. As of November 2024, the International Committee on Taxonomy of Viruses (ICTV) has identified 14,690 viral species across 3522 genera. The increasing infectious and resistance to FDA and EMA-approved antivirals, such as 300-fold efficacy reduction in Nirmatrelvir against the SARS-CoV-2 3CLpro, highlight the need for mutation-stable antivirals, likewise targeting the essential host proteins like kinases, heat shock proteins, lipid metabolism proteins, immunological pathway proteins, etc. Unlike direct-acting antivirals, HDAs reduce the risk of resistance by targeting conserved host proteins essential for viral replication. The proposal for repurposing current FDA-approved drugs for host-directed antiviral (HDA) approach is not new, such as the Ouabain, a sodium-potassium ATPase inhibitor for herpes simplex virus (HSV) and Verapamil, a calcium channel blocker for influenza A virus (IAV), to name a few. Given the colossal potential of the mutation-stable HDA approach to exterminate the virus infection, it has been increasingly studied on SARS-CoV-2. This review aims to unravel the interaction between viruses and human hosts and their successfully proposed host-directed antiviral approach to provide insight into an alternative treatment to the rampant mutation in SARS-CoV-2. The benefits, limitations, and potential of host protein-targeted antiviral therapies and their prospects are also covered in this review. Full article

The discovery and design of antiviral agents have gained unprecedented significance due to the emergence of global health threats. The use of synthetic chemistry has enabled the modification of existing molecules and the creation of entirely novel compounds. In our laboratory, we have enzymatically synthesized a novel bioconjugate, lithocholic acid oleate (LO), derived from lithocholic acid (LCA), a bile acid that has been proven by researchers to exhibit antiviral activity in vitro. The study presented herein describes the preparative synthesis, formulation, and evaluation of LO both in vitro and in vivo for its antiviral activity against human herpes simplex virus 1 (HSV-1) as a model of viral infection. Evaluation of cytotoxicity using A549 cells indicated that a combination of LO (400 μM) and LCA (30 μM) exhibited a favorable safety profile while effectively inhibiting HSV-1 infection comparable to acyclovir treatment. Furthermore, in the in vivo assay, animals treated with an oily formulation containing 7% LO; 0.50% LCA; and 3% oleic acid (OA), 48 h prior to virus exposure, showed results even superior to a 5% acyclovir commercial formulation in terms of scar formation and wound recovery. These promising results enable the development of new preventive products against HSV-1 and probably other viruses. Full article

The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented viral infections. A repository of compounds exhibiting broad-spectrum antiviral activity against a series of different viral families would be an invaluable asset to be prepared for future pandemic threats. Utilizing an open innovation crowd-sourcing paradigm, we were able to identify a compound class of diphenylureas that exhibits in vitro antiviral activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus, dengue virus, herpes, and influenza viruses. Compound 4 among the series exhibits strong activity against dengue virus, a growing global health problem with high medical need and no approved antiviral drug. The compounds are active against SARS-CoV-2 in a primary human stem cell-based mucociliary airway epithelium model and also active in vivo, as shown in a murine SARS-CoV-2 infection model. These results demonstrate the potential of the chemical class as antivirals on the one hand and the power of open innovation, crowd-sourcing, and repurposing on the other hand. Full article

Zoonotic viruses may be neglected as etiologies of meningoencephalitis in humans. We performed retrospective testing of cerebrospinal fluid from encephalitis cases in biobank material for three zoonotic or potentially zoonotic viruses: rustrela virus (Rubivirus strelense, Matonaviridae); Tahyna virus (Orthobunyavirus tahynaense, Peribunyaviridae); and lymphocytic choriomeningitis virus (“LCMV”, Mammarenavirus choriomeningitidis, Arenaviridae). The cohort consisted of 443 samples, received for routine diagnostic testing year-round between January 2019 and February 2023, and were negative for herpes simplex viruses, varicella zoster virus, and enteroviruses. Using published RT-qPCR protocols, we did not detect rustrela virus or Tahyna virus in any sample. Using a herein described RT-qPCR protocol, we detected LCMV in one sample. Partial genetic sequencing of the virus suggested that the virus was locally acquired. Our study provides information about the incidence of these viruses in humans in Austria when encephalitis is suspected. Full article

Repressor element-1 silencing transcription factor or neuron-restrictive silencer factor (REST/NRSF) is an extensively studied neuronal gene regulator both in neuronal cells and non-neuronal cells. Even though the role of REST in host cellular gene regulation is well established, its role in the establishment of viral infections and its capability to stabilize and destabilize such viral infections are scarcely studied. Co-repressor and DNA modifiers are involved in REST-mediated repressive action of its target genes. The role of REST and co-repressors together or individually in the regulation of viral as well as host genes has been unraveled in a few viruses such as HIV and influenza as well as two of the herpesvirus family members, namely herpes simplex virus type 1 (HSV-1) and Kaposi’s sarcoma-associated herpesvirus (KSHV). Here, we summarize all such virus studies involved with REST to gain a better insight into REST biology in virus infections. We also focus on unraveling the possible RE-1 binding sites in the Epstein–Barr virus (EBV) genome, a well-known human oncogenic herpesvirus that is associated with infectious mononucleosis and neoplasms such as B-cell lymphomas, nasopharyngeal carcinoma, gastric carcinoma, etc. An in silico-based approach was employed towards the prediction of such possible RE-1 binding elements in the EBV genome. This review advances the present knowledge of REST in virus infection which will aid in future efforts towards a better understanding of how REST acts in herpesviruses and other viruses for their infections and pathogenesis. Full article

Viral infections remain a major concern, as existing treatments often yield inadequate responses or lead to the development of antiviral resistance in some cases. Fucoidan extracted from Undaria pinnatifida (F) is a natural sulphated polysaccharide that exhibits antiviral action. Despite its potential, the biomedical application of F is limited due to its difficult administration through trans-mucosal, skin, or oral ingestion. The most effective way to solve these problems is to propose novel methods of administration aiming to ensure better contact between the biopolymers and pathogens, leading to their inactivation. In this work, the synthesis of films based on chitosan (Ch)-coupled F is reported, aiming to generate a synergic effect between both biopolymers in terms of their antiviral and antioxidant capability. Biocomposites were prepared by a sonochemical method. They were characterized to infer structural properties, functionality, and possible F-Ch interactions by using Zeta potential, FTIR, and XRD techniques. The biocomposites showed excellent film-forming ability. They also exhibited improved antioxidant activity with respect to F and Ch individually and proved to be non-cytotoxic. These results demonstrate, for the first time, the antiviral activity of F:Ch biocomposites against bovine coronavirus and human viruses (adenovirus, poliovirus, herpes simplex, and respiratory syncytial virus), which could be applied in film form to prevent or treat viral infections. Full article

Neurological disorders, some of which are associated with viral infections, are growing due to the aging and expanding population. Despite strong defenses of the central nervous system, some viruses have evolved ways to breach them, which often result in dire consequences. In this review, we recount the various ways by which different viruses can enter the CNS, and we describe the consequences of such invasions. Consequences may manifest as acute disease, such as encephalitis, meningitis, or result in long-term effects, such as neuromuscular dysfunction, as occurs in poliomyelitis. We discuss evidence for viral involvement in the causation of well-known chronic neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as vascular dementia in the elderly. We also describe the approaches currently available to control a few of the neural viral infections. These include antivirals that are effective against human immunodeficiency virus and herpes simplex virus, as well as vaccines valuable for controlling rabies virus, poliomyelitis virus, and some flavivirus infections. There is an urgent need to better understand, at a molecular level, how viruses contribute to acute and, especially, chronic neurological diseases and to develop more precise and effective vaccines and therapies. Full article

Recently, previously known viruses have changed their pathogenicity and encompassed new types of host populations. An example of such an infection is that caused by SARS-CoV, belonging to the “well-known” coronavirus family. Another group of viruses that are of great importance to the human population are the herpes viruses. Due to increasing viral resistance to existing antiviral drugs, plant extracts are attracting increasing interest due to their complex composition and their simultaneous attack of different viral targets. Based on the above, we tested the antiviral potential of water–alcoholic extract obtained from a commercial sample of the plant Cistus incanus L. against the enveloped viruses SvHA1, SvHA2 (ACV resistant) and HCoV 229E. The results showed both complete inhibition of the intracellular stages of the viral replication and a strong effect on extracellular virions in the three viral models. In a study of the effect on the replication of SvHA 2, the calculated selectivity index was over 10. From the experiments on the virucidal effects on the two herpes viruses, it was found that the viral titer of the samples decreased by about 4 lg compared to the control sample. The extract is of interest for introduction into practice. Full article

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored. Clinically significant cytomegalovirus (CMV) infections can affect up to 10% of patients after CAR-T, depending on the CAR-T product target, post-CAR-T complications such as cytokine release syndrome and the need for glucocorticoid therapy. Surveillance and prophylactic strategies for CMV need to be developed, whereas the risk factors for and the burden of CMV infections after BsAb are not yet well-defined. Human herpes virus 6 reactivation and end organ disease such as encephalitis are rarely reported after CAR-T and have not yet been reported after BsAb; additional research is needed. Full article

Herpes viruses are highly contagious agents affecting all classes of vertebrates, thus causing serious health, social, and economic losses. Within the One Health concept, novel therapeutics are extensively studied for both veterinary and human control and management of the infection, but the optimal strategy has not been invented yet. Lactic acid bacteria are key components of the microbiome that are known to play a protective role against pathogens as one of the proposed mechanisms involves compounds released from their metabolic activity. Previously, we reported the anti-herpes effect of postmetabolites isolated from Lactobacilli, and here, we confirm the inhibitory properties of another nine products against the phylogenetically distant human Herpes simplex virus-1 (HSV-1) and fish Koi Herpes virus (KHV) in cell cultures. Cytotoxicity, cytopathic effect inhibition, virucidal effect, the influence on the adsorption stage of the virus to the cells, as well as the protective effect of the postmetabolites on healthy cells were evaluated. The inhibitory effect was more pronounced against HSV-1 than against KHV at all studied viral cycle stages. Regarding the intracellular replicative steps, samples S7, S8, and S9 (Mix group) isolated from Ligilactobacillus salivarius (vaginal strain) demonstrated the most distinct effect with calculated selective indices (SIs) in the range between 69.4 and 77.8 against HSV-1, and from 62.2 to 68.4 against KHV. Bioactive metabolites from various LAB species significantly inhibit extracellular HSV-1 and, to a lesser extent, KHV virions. The blockage of viral adsorption to the host cells was remarkable, as recorded by a decrease in the viral titer with Δlg ≥ 5 in the Mix group for both herpes viruses. The remaining postmetabolites also significantly inhibited viral adsorption to varying degrees with Δlg ≥ 3. Most metabolites also exerted a protective effect on healthy MDBK and CCB cells to subsequent experimental viral infection. Our results reveal new horizons for the application of LAB and their postbiotic products in the prevention and treatment of herpes diseases. Full article

Photodynamic inactivation (PDI) has been revealed as a valuable approach against viral infections because of the fast therapeutic effect and low possibility of resistance development. The photodynamic inhibition of the infectivity of human herpes simplex virus type 1 (HSV-1) strain Victoria at different stages of its reproduction was studied. PDI activity was determined on extracellular virions, on the stage of their adsorption to the Madin-Darby bovine kidney (MDBK) cell line and inhibition of the viral replication stage by application of two tetra-methylpyridiloxy substituted gallium and zinc phthalocyanines (ZnPcMe and GaPcMe) upon 660 nm light exposure with a light-emitting diode (LED 660 nm). The PDI effect was evaluated on extracellular virions and virus adsorption by the terminal dilution method and the change in viral infectivity, which was compared to the untreated control group. The decrease in viral titer (Δlgs) was determined. The effect on the replicative cycle of the virus was determined using the cytopathic effect inhibition (CPE) assay. The direct influence on the virions showed a remarkable effect with a decrease in the viral titer more than 4 (Δlg > 4). The influence of the virus to the cell on the stage of adsorption was also significantly affected by the exposure time and the concentration of applied photosensitizers. A distinct inhibition was evaluated for ZnPcMe at the viral replication stage, which demonstrated a high photoinactivation index (PII = 33.0). This study suggested the high efficacy of PDI with phthalocyanines on HSV-1 virus, with full inhibition caused by the mechanism of singlet oxygen generation. These promising data are a good basis for further investigations on the PDI application against pathogenic viruses. Full article

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet. Full article

Gene therapies hold significant promise for treating previously incurable diseases. A number of gene therapies have already been approved for clinical use. Currently, gene therapies are mostly limited to the use of adeno-associated viruses and the herpes virus. Viral vectors, particularly those derived from human viruses, play a critical role in this therapeutic approach due to their ability to efficiently deliver genetic material to target cells. Despite their advantages, such as stable gene expression and efficient transduction, viral vectors face numerous limitations that hinder their broad application. These limitations include small cloning capacities, immune and inflammatory responses, and risks of insertional mutagenesis. This review explores the current landscape of viral vectors used in gene therapy, discussing the different types of DNA- and RNA-based viral vectors, their characteristics, limitations, and current medical and potential clinical applications. The review also highlights strategies to overcome existing challenges, including optimizing vector design, improving safety profiles, and enhancing transgene expression both using molecular techniques and nanotechnologies, as well as by approved drug formulations. Full article

The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, advanced forward and reverse genetic tools, and suitability for chemical screening studies. Despite anatomical differences with humans, the zebrafish model has proven instrumental in investigating immune responses and human infectious diseases. Notably, zebrafish larvae rely exclusively on innate immune responses during the early stages of development, as the adaptive immune system becomes fully functional only after 4–6 weeks post-fertilization. This window provides a unique opportunity to isolate and examine infection and inflammation mechanisms driven by the innate immune response without the confounding effects of adaptive immunity. In this review, we highlight the strengths and limitations of using zebrafish as a powerful vertebrate model to study innate immune responses in infectious diseases. We will particularly focus on host-pathogen interactions in human infections caused by various bacteria (Clostridioides difficile, Staphylococcus aureus, and Pseudomonas aeruginosa), viruses (herpes simplex virus 1, SARS-CoV-2), and fungi (Aspergillus fumigatus and Candida albicans). Full article