Neonatal Herpes simplex virus (HSV) infections are rare but potentially fatal diseases. HSV infection is usually acquired when a newborn comes into contact with viable virus during intrapartum transit through infected birth canal. However, some cases are transmitted postnatally. Disseminated HSV infection with multiorgan involvement is the most feared form of the disease and is burdened with high morbidity and mortality. In this case report, we present a case of unexpected death of a neonate in whom the autopsy revealed disseminated Herpes simplex virus 1 (HSV1) infection.

• Klíčová slova
• HSV1, autory, disseminated infection, herpes simplex 1, new-born child, newborn, research,
• MeSH
• fatální výsledek MeSH
• herpes simplex * patologie   MeSH
• infekční komplikace v těhotenství patologie   virologie   MeSH
• lidé MeSH
• lidský herpesvirus 1 * MeSH
• novorozenec MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.

• Klíčová slova
• HSV life cycle, HSV-1, HSV-2, antiviral properties, cellular pathways, drug resistance, flavonoids, herpes simplex virus, host–virus interaction, natural antivirals, natural products,
• MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• flavonoidy farmakologie   terapeutické užití   MeSH
• herpes simplex * farmakoterapie   MeSH
• lidé MeSH
• lidský herpesvirus 1 * fyziologie   MeSH
• stadia vývoje MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH
• flavonoidy MeSH

Amphipathic perylene derivatives are broad-spectrum antivirals against enveloped viruses that act as fusion inhibitors in a light-dependent manner. The compounds target the lipid bilayer of the viral envelope using the lipophilic perylene moiety and photogenerating singlet oxygen, thereby causing damage to unsaturated lipids. Previous studies show that variation of the polar part of the molecule is important for antiviral activity. Here, we report modification of the lipophilic part of the molecule, perylene, by the introduction of 4-, 8-, and 12-carbon alkyls into position 9(10) of the perylene residue. Using Friedel-Crafts acylation and Wolff-Kishner reduction, three 3-acetyl-9(10)-alkylperylenes were synthesized from perylene and used to prepare 9 nucleoside and 12 non-nucleoside amphipathic derivatives. These compounds were characterized as fluorophores and singlet oxygen generators, as well as tested as antivirals against herpes virus-1 (HSV-1) and vesicular stomatitis virus (VSV), both known for causing superficial skin/mucosa lesions and thus serving as suitable candidates for photodynamic therapy. The results suggest that derivatives with a short alkyl chain (butyl) have strong antiviral activity, whereas the introduction of longer alkyl substituents (n = 8 and 12) to the perylenyethynyl scaffold results in a dramatic reduction of antiviral activity. This phenomenon is likely attributable to the increased lipophilicity of the compounds and their ability to form insoluble aggregates. Moreover, molecular dynamic studies revealed that alkylated perylene derivatives are predominately located closer to the middle of the bilayer compared to non-alkylated derivatives. The predicted probability of superficial positioning correlated with antiviral activity, suggesting that singlet oxygen generation is achieved in the subsurface layer of the membrane, where the perylene group is more accessible to dissolved oxygen.

• Klíčová slova
• antivirals, lipophilicity, perylene, photosensitizers, singlet oxygen,
• MeSH
• antivirové látky farmakologie   chemie   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky farmakologie   MeSH
• lidský herpesvirus 1 * MeSH
• perylen * farmakologie   MeSH
• singletový kyslík MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• fotosenzibilizující látky MeSH
• perylen * MeSH
• singletový kyslík MeSH

PURPOSE: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

• MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• lidský herpesvirus 1 * MeSH
• melanom * farmakoterapie   MeSH
• onkolytická viroterapie * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• pembrolizumab MeSH Prohlížeč
• talimogene laherparepvec MeSH Prohlížeč

Chronic hepatitis B (CHB) remains a major public health problem worldwide, with limited treatment options, but inducing an antiviral response by innate immunity activation may provide a therapeutic alternative. We assessed the cytokine-mediated anti-hepatitis B virus (HBV) potential for stimulating the cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway using STING agonists in primary human hepatocytes (PHH) and nonparenchymal liver cells (NPCs). The natural STING agonist, 2',3'-cyclic GMP-AMP, the synthetic analogue 3',3'-c-di(2'F,2'dAMP), and its bis(pivaloyloxymethyl) prodrug had strong indirect cytokine-mediated anti-HBV effects in PHH regardless of HBV genotype. Furthermore, STING agonists induced anti-HBV cytokine secretion in vitro, in both human and mouse NPCs, and triggered hepatic T cell activation. Cytokine secretion and lymphocyte activation were equally stimulated in NPCs isolated from control and HBV-persistent mice. Therefore, STING agonists modulate immune activation regardless of HBV persistence, paving the way toward a CHB therapy.

• Klíčová slova
• Chronic Hepatitis B, HBV-persistent mouse model, STING, antiviral immunity, cytokine, nonparenchymal liver cells,
• MeSH
• cytokiny metabolismus   MeSH
• hepatitida B * farmakoterapie   MeSH
• hepatocyty MeSH
• herpesvirus B * MeSH
• interferony metabolismus   MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• interferony MeSH

Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, and most of these viruses are neurotropic, with the capacity to generate severe and chronic neurological diseases of the peripheral nervous system (PNS) and central nervous system (CNS). Treatment of HHV infections based on strategies that include natural products-derived drugs is one of the most rapidly developing fields of modern medicine. Therefore, in this paper, we lend insights into the recent advances that have been achieved during the past five years in utilizing flavonoids as promising natural drugs for the treatment of HHVs infections of the nervous system such as alpha-herpesviruses (herpes simplex virus type 1, type 2, and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus). The neurological complications associated with infections induced by the reviewed herpesviruses are emphasized. Additionally, this work covers all possible mechanisms and pathways by which flavonoids induce promising therapeutic actions against the above-mentioned herpesviruses.

• Klíčová slova
• Epstein–Barr virus, HSV-1, HSV-2, Kaposi sarcoma-associated herpesvirus, flavonoids, herpes simplex virus, human cytomegalovirus, mechanisms of action, nervous system, neurological diseases, varicella-zoster virus,
• MeSH
• centrální nervový systém MeSH
• flavonoidy farmakologie   terapeutické užití   MeSH
• herpetické infekce * farmakoterapie   MeSH
• infekce virem Epsteina-Barrové * MeSH
• lidé MeSH
• lidský herpesvirus 1 * genetika   MeSH
• virus Epsteinův-Barrové genetika   MeSH
• virus varicella zoster genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• flavonoidy MeSH

Serious burn trauma is associated with changes of the immune system, and immunosuppression induced by burn trauma can lead to reactivation of latent infections. Herpetic viruses are known for their lifelong persistence after primary infection and ability to reactivate. Their reactivation in the setting of burn trauma or primary infection can cause serious complications for a weakened burn patient. Presented is a case of a toddler who sustained second-degree scald burns over 20% of his body surface area. The injury was complicated by a multi-resistant bacterial infection in addition to reactivation of a latent HHV-6 infection concurrently with a primary HSV-1 infection. Described further are basic diagnostics, local and systemic treatment strategies, and other complications due to disseminated herpetic infections. To date, HHV-6 reactivation has not been described in conjunction with burn injury.

• Klíčová slova
• HHV-6, HSV-1, Pediatric burn trauma, herpes virus infection,
• MeSH
• aktivace viru fyziologie   MeSH
• bakteriální infekce etiologie   mikrobiologie   MeSH
• herpetické infekce etiologie   virologie   MeSH
• lidé MeSH
• lidský herpesvirus 1 izolace a purifikace   MeSH
• lidský herpesvirus 6 izolace a purifikace   MeSH
• mnohočetná bakteriální léková rezistence fyziologie   MeSH
• popálení komplikace   patofyziologie   MeSH
• předškolní dítě MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• acyklovir * farmakologie   MeSH
• DNA-dependentní DNA-polymerasy MeSH
• exodeoxyribonukleasy MeSH
• mutace MeSH
• Simplexvirus * genetika   MeSH
• virové proteiny MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• acyklovir * MeSH
• DNA polymerase, Simplexvirus MeSH Prohlížeč
• DNA-dependentní DNA-polymerasy MeSH
• exodeoxyribonukleasy MeSH
• virové proteiny MeSH

Based on seroepidemiological studies, human herpes simplex virus types 1 and 2 (HSV-1, HSV-2) are put in relation with a number of cancer diseases; however, they do not appear to play a direct role, being only considered cofactors. Their ability to transform the cells in vitro could be demonstrated experimentally by removing their high lytic ability by a certain dose of UV radiation or by photoinactivation in the presence of photosensitizers, such as neutral red or methylene blue, or culturing under conditions suppressing their lytic activity. However, recent studies indicate that UV irradiated or photoinactivated HSV-1 and HSV-2, able to transform non-transformed cells, behave differently in transformed cells suppressing their transformed phenotype. Furthermore, both transforming and transformed phenotype suppressing activities are pertaining only to non-syncytial virus strains. There are some proposed mechanisms explaining their transforming activity. According to the "hit and run" mechanism, viral DNA induces only initiation of transformation by interacting with cellular DNA bringing about mutations and epigenetic changes and is no longer involved in other processes of neoplastic progression. According to the "hijacking" mechanism, virus products in infected cells may activate signalling pathways and thus induce uncontrolled proliferation. Such a product is e.g. a product of HSV-2 gene designated ICP10 that encodes an oncoprotein RR1PK that activates the Ras pathway. In two cases of cancer, in the case of serous ovarian carcinoma and in some prostate tumours, virus-encoded microRNAs (miRNAs) were detected as a possible cofactor in tumorigenesis. And, recently described herpes virus-associated growth factors with transforming and transformation repressing activity might be considered important factors playing a role in tumour formation. And finally, there is a number of evidence that HSV-2 may increase the risk of cervical cancer after infection with human papillomaviruses. A similar situation is with human cytomegalovirus; however, here, a novel mechanism named oncomodulation has been proposed. Oncomodulation means that HCMV infects tumour cells and modulates their malignant properties without having a direct effect on cell transformation.

• MeSH
• DNA virů genetika   MeSH
• herpetické infekce komplikace   virologie   MeSH
• lidé MeSH
• lidský herpesvirus 1 genetika   patogenita   MeSH
• lidský herpesvirus 2 genetika   patogenita   MeSH
• nádory virologie   MeSH
• virová transformace buněk genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA virů MeSH

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

• Klíčová slova
• antiherpetic drugs, bioactive natural products, drug development, drug resistance, herpes simplex virus infection, mechanisms of action, preclinical and clinical studies,
• MeSH
• antivirové látky chemie   farmakologie   MeSH
• biologické přípravky chemie   farmakologie   MeSH
• farmaceutický průmysl MeSH
• lidé MeSH
• lidský herpesvirus 1 účinky léků   MeSH
• lidský herpesvirus 2 účinky léků   MeSH
• objevování léků * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH
• biologické přípravky MeSH