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.

• 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

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

• MeSH
• DNA virů izolace a purifikace   MeSH
• lidský herpesvirus 1 izolace a purifikace   MeSH
• lidský herpesvirus 2 izolace a purifikace   MeSH
• reagenční diagnostické soupravy virologie   MeSH
• testování odbornosti laboratoří MeSH
• virus varicella zoster izolace a purifikace   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.

• 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

• MeSH
• Acinetobacter baumannii patogenita   MeSH
• acitretin aplikace a dávkování   MeSH
• acyklovir terapeutické užití   MeSH
• biopsie MeSH
• Corynebacterium patogenita   MeSH
• Darierova nemoc * diagnóza   komplikace   patologie   MeSH
• erytém etiologie   MeSH
• foskarnet aplikace a dávkování   MeSH
• horečka etiologie   MeSH
• hydrokortison aplikace a dávkování   MeSH
• Kaposiho erupce variceliformní etiologie   farmakoterapie   patologie   virologie   MeSH
• Klebsiella pneumoniae patogenita   MeSH
• kombinace léků piperacilin a tazobactam terapeutické užití   MeSH
• léková rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský herpesvirus 1 patogenita   MeSH
• meropenem aplikace a dávkování   MeSH
• neúspěšná terapie MeSH
• oxacilin terapeutické užití   MeSH
• pneumonie etiologie   komplikace   virologie   MeSH
• progrese nemoci MeSH
• umělé dýchání MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Praktičtí lékaři se velmi často setkávají s pacienty s opakovanými projevy nemocí, které jsou označovány jako nemoci z nachlazení, které mají u některých pacientů tendenci se vracet nebo je jejich průběh protrahovaný. Součástí běžné praxe jsou i pacienti s recidivujícími herpetickými výsevy, pacienti s častými angínami, záněty průdušek či urologickými potížemi. U řady pacientů bývá obvykle velmi častým steskem výrazná únava, subfebrilie, nespecifické bolesti kloubů a svalů nebo projevy uzlinového syndromu. Na tomto stavu se mohou podílet virová, bakteriální či mykotická agens, ale i charakter životosprávy a psychosomatika. Recidivující infekce také mohou být příznakem závažných imunodeficiencí. V dospělém věku je třeba zvážit možnost některé z primárních imunodeficiencí či imunodeficience sekundární, doprovázející pacienty na imunosupresivní léčbě, onkologicky nemocné a další.

General practitioners usually meet patients with recurrent episodes of disorders characterized as common cold disease. These disorders can be seen repeatedly or their course may be prolonged. Repeated herpetic infections, tonsillitis, cough and urologic disorders are also the reason for frequent visits of general practitioners. Typical symptoms include fatigue, fever, non-specific arthralgia or myalgia or enlargement of lymph nodes. Triggers can be viruses, bacterial or fungal infection but also lifestyle and psychosomatic problems. Recurrent infections are also symptoms of immunodeficiency. Primary immunodeficiency as a common variable immunodeficiency can be firstly diagnose at adulthood. Secondary immunodeficiency accompanied more frequently patients with immunosuppressive therapy, oncologic treatment and others.

• MeSH
• Alphapapillomavirus klasifikace   patogenita   MeSH
• antivirové látky aplikace a dávkování   MeSH
• autovakcíny terapeutické užití   MeSH
• bakteriální infekce diagnóza   etiologie   farmakoterapie   klasifikace   prevence a kontrola   MeSH
• bradavice etiologie   farmakoterapie   prevence a kontrola   MeSH
• diferenciální diagnóza MeSH
• herpes genitalis diagnóza   etiologie   farmakoterapie   MeSH
• herpes labialis diagnóza   etiologie   farmakoterapie   MeSH
• herpes zoster diagnóza   etiologie   terapie   MeSH
• inosin pranobex aplikace a dávkování   MeSH
• kašel etiologie   farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• lidský herpesvirus 1 patogenita   MeSH
• lidský herpesvirus 2 patogenita   MeSH
• nemoci imunitního systému diagnóza   etiologie   MeSH
• recidiva * MeSH
• rýma diagnóza   etiologie   farmakoterapie   klasifikace   prevence a kontrola   MeSH
• Simplexvirus patogenita   MeSH
• vakcíny terapeutické užití   MeSH
• virové nemoci * diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• virus Epsteinův-Barrové patogenita   MeSH
• virus varicella zoster patogenita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Souhrn: Herpetická ezofagitida je onemocnění diagnostikované zejména u imunokompromitovaných pacientů. U imunokompetentních jedinců se jedná o vzácné onemocnění, na které je ale třeba pomýšlet při akutně vzniklé triádě potíží – odynofagie, bolesti na hrudi a horečka nejasného původu. Nejčastějším původcem je herpes simplex virus typu 1 (HSV1). Ve většině případů vzniká onemocnění reaktivací latentní infekce HSV1, vzácněji při primoinfekci. Základem diagnostiky je endoskopické vyšetření jícnu s provedením biopsie a přímým průkazem přítomnosti viru v bioptickém vzorku. U imunokompromitovaných pacientů je vždy indikována léčba acyklovirem, který je v této indikaci virostatikem první volby. U imunokompetentních pacientů se jedná o tzv. selflimiting onemocnění, kdy v naprosté většině případů postačuje symptomatická léčba. Kazuistika popisuje imunokompetentního pacienta s náhle vzniklou typickou triádou potíží způsobených herpetickou ezofagitidou. Diagnóza byla potvrzena průkazem přítomnosti virové DNA metodou PCR ze vzorku odebraného při endoskopickém vyšetření. Vzhledem k těžšímu průběhu onemocnění byl pacient přeléčen acyklovirem a došlo k rychlé úpravě celkového stavu i lokálního endoskopického nálezu.

Summary: Herpetic esophagitis is a disease diagnosed especially in immunocompromised patients. Although the disease is rare in immunocompetent individuals, the diagnosis should be considered in the presence of its acute triad of clinical symptoms – odynophagia, chest pain, and fever of unknown origin. Herpes simplex virus type 1 (HSV1) is the most common causative agent. In the majority of cases, the disease develops by re-activation of latent HSV1 infection or, rather rarely, by primo-infection. The basis of diagnosis is endoscopic examination of the esophagus with biopsy and direct detection of the virus in the bioptic sample. In immunocompromised patients, treatment with acyclovir, which is the first-line virostatic in this indication, is always indicated. In immunocompetent patients, this is a self-limiting disease, where in most cases merely symptomatic treatment is sufficient. This case report describes an immunocompetent patient with a suddenly occurring typical triad of symptoms caused by herpetic esophagitis. The diagnosis was confirmed by the presence of viral DNA as determined by polymerase chain reaction from a sample taken during endoscopic examination. Due to the more severe course of the disease, the patient was treated with acyclovir and the general condition and local endoscopic findings then quickly improved.

• Klíčová slova
• herpetická ezofagitida,
• MeSH
• acyklovir terapeutické užití   MeSH
• dítě MeSH
• endoskopie metody   MeSH
• ezofagitida * etiologie   mikrobiologie   terapie   MeSH
• herpetické infekce komplikace   MeSH
• lidé MeSH
• lidský herpesvirus 1 izolace a purifikace   MeSH
• polymerázová řetězová reakce metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• inhibitory kontrolních bodů * farmakologie   terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa-2 terapeutické užití   MeSH
• ipilimumab terapeutické užití   MeSH
• klinické zkoušky kontrolované jako téma MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• lidský herpesvirus 1 MeSH
• melanom * farmakoterapie   radioterapie   terapie   MeSH
• metastázy nádorů terapie   MeSH
• nádory mozku sekundární   MeSH
• neoadjuvantní terapie metody   MeSH
• nivolumab terapeutické užití   MeSH
• onkolytická viroterapie metody   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-raf antagonisté a inhibitory   MeSH
• recidiva MeSH
• Check Tag
• lidé 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

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.

• 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