Search Results (332)

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Background/Objectives: The aetiology of Bell’s palsy remains unclear and is typically diagnosed by exclusion. This study investigated the potential role of neurotropic viruses and explored the relationship between facial nerve impairment and vestibular dysfunction to improve the understanding of the condition. Methods: Antibodies against herpes simplex virus (HSV) and varicella-zoster virus (VZV) were assessed using ELISA. Vestibular function was evaluated through computerised videonystagmography, rotatory chair, and clinical vestibulospinal assessments. Facial nerve lesion localisation was determined by stapedial reflex testing. Fisher’s exact test was used for statistical analysis. Results: Of 51 patients with Bell’s palsy, 62.7% exhibited vestibular dysfunction, and 70.6% were IgG-positive for at least one neurotropic virus. Vestibular impairment was significantly more common in seropositive patients. Statistically significant associations were observed between vestibular dysfunction and viral IgG seropositivity (p < 0.0001), the severity of vestibular dysfunction and facial paresis (p = 0.0126), and the side of vestibular impairment and the side of facial palsy (p < 0.0001), with 90.6% of cases showing ipsilateral involvement. Conclusions: These findings support the hypothesis that neurotropic viruses may act as a common pathological factor in both Bell’s palsy and associated vestibular dysfunction. Full article

The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated to mature neurons. In this paper, we present a new method for differentiating one such model, the Lund human mesencephalic (LUHMES) dopaminergic neurons. This method is two days faster than some established protocols, results in nearly five times greater numbers of mature neurons, and involves fewer handling steps that could introduce technical variability. Moreover, it overcomes the problem of cell aggregate formation that commonly impedes high-resolution imaging, cell dissociation, and downstream analysis. While recently established for herpes simplex virus type 1, we demonstrate that LUHMES neurons can facilitate studies of other herpesviruses, as well as RNA viruses associated with childhood encephalitis and hemorrhagic fever. This protocol provides an improvement in the generation of large-scale neuronal cultures, which may be readily applicable to other neuronal 2D cell culture models and provides a system for studying neurotrophic viruses. We named this method the Streamlined Protocol for Enhanced Expansion and Differentiation Yield, or SPEEDY, method. Full article

Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article

Rapid, safe, and field-deployable molecular diagnostics are crucial for the effective management of infectious disease outbreaks, particularly those involving highly infectious pathogens, which can produce clinical symptoms similar to less infectious pathogens, thus raising potential biosafety concerns. In this study, we evaluated DNA/RNA Defend Pro (DRDP) buffer, a novel viral-inactivating transport medium designed to stabilize nucleic acids and allow direct PCR without nucleic acid extraction. To ensure critical qPCR parameters were not compromised by using DRDP, we conducted serial dilution tests using herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV), comparing DRDP to standard universal transport medium (UTM). Detection sensitivity, determined by cycle quantification (Cq) values, favored DRDP, as UTM samples required a 2–3-fold dilution to mitigate PCR inhibition. DRDP maintained reliable PCR compatibility at reaction volumes containing up to 25% buffer. At higher DRDP concentrations (30–35%), PCR inhibition occurred due to EDTA content but was fully reversible by adding supplemental magnesium. Furthermore, DRDP samples did not require an initial 95 °C thermal lysis step, thus simplifying the procedure without reducing PCR sensitivity or efficiency. Full article

Checkpoint inhibitor therapy revolutionized the treatment of patients with melanoma. However, in patients where melanoma exhibits resistance to checkpoint inhibitor therapy, the treatment options are limited. Oncolytic viruses are a unique form of immunotherapy that uses live viruses to infect and lyse tumor cells to release the elusive neoantigen picked up by the antigen-presenting cells, thus increasing the chances of an immune response against cancer. Coupled with checkpoint inhibitors, intratumoral injections of the oncolytic virus can help an enhanced immune response, especially in a tumor that displays resistance to checkpoint inhibitors. However, oncolytic viruses are not bereft of challenges and face several obstacles in the tumor microenvironment. From the historical use of wild viruses to the sophisticated use of genetically modified viruses in the current era, oncolytic virus therapy has evolved tremendously in the last two decades. Increasing the ability of the virus to select the malignant cells over the non-malignant ones, circumventing the antiviral immune response from the body, and enhancing the oncolytic properties of the viral platform by attaching various ligands are some of the several improvements made in the last three decades. In this manuscript, we trace the journey of the development of oncolytic virus therapy, especially in the context of melanoma. We review the clinical trials of talimogene laherparepvec in patients with melanoma. We also review the data available from the clinical trials of vusolimogene oderparepvec in patients with melanoma. Finally, we review the use of various oncolytic viruses and their challenges in clinical development. This manuscript aims to create a comprehensive literature review for clinicians to understand and implement oncolytic virus therapy in patients diagnosed with melanoma. Full article

Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle. Full article

Viral infections may vary from mild to severe, manifesting with a wide range of symptoms, including skin lesions, influenza-like symptoms, or meningitis/meningoencephalitis signs. Viruses that cause both skin lesions and meningitis comprise, e.g., Enteroviruses (EVs) and Herpes viruses (HV). EVs are responsible for approximately 90% of viral meningitis cases. They occur frequently among children under 3 years of age and are characterized by various types of rash. HV infections are responsible for up to 18% of viral meningitis, mostly among adults or older children. Most patients with viral meningitis recover entirely. However, the rates of serious complications and mortality may be as high as 74% and 10%, respectively, for particularly vulnerable neonatal or immunocompromised patients. Patients that present signs of encephalitis and/or are suspected to have HSV/VZV infection require immediate implementation of empiric acyclovir therapy before receiving the polymerase chain reaction (PCR) test results. The clinical picture of viral meningitis may differ depending on the virus, including the presence of both meningeal signs and skin lesions. Therefore, early identification of the etiological factor is necessary for early and proper treatment implementation. It is crucial to accurately differentiate between the causative agents, and this work focuses on answering the question of how skin lesions can assist in achieving a better and faster diagnosis. The aim of this review was to analyze the characteristics of skin lesions in the course of meningitis caused by various viral species. This can be helpful for physicians in the diagnostic process and subsequent treatment. Full article

This review provides an updated overview of oncolytic virotherapy as a promising therapeutic strategy for colorectal cancer (CRC), focusing on six key viral platforms: adenovirus, herpes simplex virus (HSV), reovirus, vesicular stomatitis virus (VSV), vaccinia virus (VV), and measles virus (MV). These viruses exhibit tumor-selective replication and exert their effects through mechanisms such as direct oncolysis, the delivery of immunostimulatory genes (e.g., IL-12, IL-15, GM-CSF), the activation of innate and adaptive immune responses, and the remodeling of the tumor microenvironment. Preclinical and early clinical studies suggest that oncolytic viruses can enhance the efficacy of existing treatments, particularly in immunologically “cold” tumors such as microsatellite stable CRC, when used in combination with chemotherapy or immune checkpoint inhibitors. Despite encouraging results, several challenges remain, including antiviral immune clearance, tumor heterogeneity, and limitations in systemic delivery. Current research focuses on improving viral engineering, enhancing tumor targeting, and designing combinatorial strategies to overcome resistance and maximize clinical benefits. Overall, oncolytic viruses represent a versatile and evolving therapeutic class with the potential to address unmet clinical needs in CRC. Full article

Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. Unfortunately, mutations have already emerged that confer resistance to these antivirals. In addition, there is an urgent need for broad-spectrum antivirals to address the unpredictable emergence of new viruses with pandemic potential. One promising strategy involves modulating the innate immune response and cellular signaling. Imiquimod, a Toll-like receptor 7 (TLR7) agonist, has shown efficacy in murine models of influenza and respiratory syncytial virus (RSV). Additionally, it demonstrates antiviral activity against herpes simplex virus type 1 (HSV-1) and RSV independent of the TLR7/nuclear factor kappa B (NF-κB) pathway, with protein kinase A (PKA) as a crucial downstream effector. In this study, we demonstrate that imiquimod exhibits concentration-dependent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and canine coronavirus (CCoV) in epithelial cells, underscoring its broad-spectrum action against coronaviruses. Moreover, its anti-coronavirus effect appears to be independent of the TLR/NF-κB and PKA/exchange protein directly activated by cyclic adenosine monophosphate (EPAC) pathways and may instead be linked to the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The ability of imiquimod to inhibit coronavirus replication via the MEK/ERK pathway, coupled with its immunomodulatory properties, highlights its potential as a broad-spectrum antiviral. Full article

Encephalitis, a severe neurological condition caused by human-to-human (H2H) transmitted viruses, such as herpes simplex virus (HSV), requires a rigorous mathematical framework to understand its transmission dynamics. This study develops a nonlinear compartmental model, SEITR (Susceptible–Exposed–Infected–Treated–Recovered), to characterize the progression of viral encephalitis. The basic reproduction number (R₀) is derived using the next-generation matrix method, serving as a threshold parameter determining disease persistence. The local and global stability of the disease-free and endemic equilibria are established through a rigorous mathematical analysis. Additionally, a sensitivity analysis quantifies the impact of key parameters on R₀, offering more profound insights into their mathematical significance. Numerical simulations validate the theoretical results, demonstrating the system’s dynamical behavior under varying epidemiological conditions. This study provides a mathematically rigorous approach to modeling viral encephalitis transmission, filling a gap in the literature and offering a foundation for future research in infectious disease dynamics. Full article

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

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