Psoromic acid (PA), a bioactive lichen-derived compound, was investigated for its inhibitory properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), along with the inhibitory effect on HSV-1 DNA polymerase, which is a key enzyme that plays an essential role in HSV-1 replication cycle. PA was found to notably inhibit HSV-1 replication (50% inhibitory concentration (IC50): 1.9 μM; selectivity index (SI): 163.2) compared with the standard drug acyclovir (ACV) (IC50: 2.6 μM; SI: 119.2). The combination of PA with ACV has led to potent inhibitory activity against HSV-1 replication (IC50: 1.1 µM; SI: 281.8) compared with that of ACV. Moreover, PA displayed equivalent inhibitory action against HSV-2 replication (50% effective concentration (EC50): 2.7 μM; SI: 114.8) compared with that of ACV (EC50: 2.8 μM; SI: 110.7). The inhibition potency of PA in combination with ACV against HSV-2 replication was also detected (EC50: 1.8 µM; SI: 172.2). Further, PA was observed to effectively inhibit HSV-1 DNA polymerase (as a non-nucleoside inhibitor) with respect to dTTP incorporation in a competitive inhibition mode (half maximal inhibitory concentration (IC50): 0.7 μM; inhibition constant (Ki): 0.3 μM) compared with reference drugs aphidicolin (IC50: 0.8 μM; Ki: 0.4 μM) and ACV triphosphate (ACV-TP) (IC50: 0.9 μM; Ki: 0.5 μM). It is noteworthy that the mechanism by which PA-induced anti-HSV-1 activity was related to its inhibitory action against HSV-1 DNA polymerase. Furthermore, the outcomes of in vitro experiments were authenticated using molecular docking analyses, as the molecular interactions of PA with the active sites of HSV-1 DNA polymerase and HSV-2 protease (an essential enzyme required for HSV-2 replication) were revealed. Since this is a first report on the above-mentioned properties, we can conclude that PA might be a future drug for the treatment of HSV infections as well as a promising lead molecule for further anti-HSV drug design.

• Klíčová slova
• HSV, HSV replication, anti-enzymatic properties, antiherpetic, lichen metabolites, psoromic acid,
• MeSH
• antivirové látky * chemie   farmakologie   MeSH
• benzoxepiny * chemie   farmakologie   MeSH
• Cercopithecus aethiops MeSH
• DNA-dependentní DNA-polymerasy * chemie   metabolismus   MeSH
• inhibitory syntézy nukleových kyselin chemie   farmakologie   MeSH
• kyseliny karboxylové * chemie   farmakologie   MeSH
• lidé MeSH
• lidský herpesvirus 1 fyziologie   MeSH
• lidský herpesvirus 2 fyziologie   MeSH
• lišejníky chemie   MeSH
• replikace viru účinky léků   MeSH
• simulace molekulového dockingu * MeSH
• Vero buňky MeSH
• virové proteiny * antagonisté a inhibitory   chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky * MeSH
• benzoxepiny * MeSH
• DNA-dependentní DNA-polymerasy * MeSH
• inhibitory syntézy nukleových kyselin MeSH
• kyseliny karboxylové * MeSH
• psoromic acid MeSH Prohlížeč
• virové proteiny * MeSH

For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL-1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL-1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

• Klíčová slova
• ESI-mass spectrometry-based assay, Hibiscus sabdariffa L., anti-HSV-2 activity, bacterial infection, protocatechuic acid, urease inhibitors,
• MeSH
• acyklovir farmakologie   MeSH
• antivirové látky chemie   izolace a purifikace   farmakologie   MeSH
• Cercopithecus aethiops MeSH
• Hibiscus chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• inhibiční koncentrace 50 MeSH
• inhibitory enzymů chemie   izolace a purifikace   farmakologie   MeSH
• kinetika MeSH
• lidský herpesvirus 2 účinky léků   MeSH
• polyfenoly chemie   izolace a purifikace   farmakologie   MeSH
• preklinické hodnocení léčiv MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   MeSH
• ureasa antagonisté a inhibitory   chemie   MeSH
• Vero buňky MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• inhibitory enzymů MeSH
• polyfenoly MeSH
• rostlinné extrakty MeSH
• ureasa MeSH

Long COVID, in which disease-related symptoms persist for months after recovery, has led to a revival of the discussion of whether neuropsychiatric long-term symptoms after viral infections indeed result from virulent activity or are purely psychological phenomena. In this review, we demonstrate that, despite showing differences in structure and targeting, many viruses have highly similar neuropsychiatric effects on the host. Herein, we compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus 1 (HIV-1), Ebola virus disease (EVD), and herpes simplex virus 1 (HSV-1). We provide evidence that the mutual symptoms of acute and long-term anxiety, depression and post-traumatic stress among these viral infections are likely to result from primary viral activity, thus suggesting that these viruses share neuroinvasive strategies in common. Moreover, it appears that secondary induced environmental stress can lead to the emergence of psychopathologies and increased susceptibility to viral (re)infection in infected individuals. We hypothesize that a positive feedback loop of virus-environment-reinforced systemic responses exists. It is surmised that this cycle of primary virulent activity and secondary stress-induced reactivation, may be detrimental to infected individuals by maintaining and reinforcing the host's immunocompromised state of chronic inflammation, immunological strain, and maladaptive central-nervous-system activity. We propose that this state can lead to perturbed cognitive processing and promote aversive learning, which may manifest as acute, long-term neuropsychiatric illness.

• Klíčová slova
• HIV-1, SARS virus, interoception, neuropsychiatry, virus latency,
• Publikační typ
• časopisecké články MeSH
• přehledy 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

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

In recent years, the rate of genital infections caused by Herpes simplex virus types 1 and 2 (HSV-1, HSV-2) has increased. Following primary infection with HSV-2, recurrent genital herpes (GH) often develops or asymptomatic virus shedding occurs. HSV-1-induced GH recurrencies are significantly less frequent. The options for diagnosing HSV infections have improved markedly: they include determination of type-specific antibodies in the blood (anti-HSV-1 and anti-HSV-2), culture of HSV from lesions or detection of viral antigens by immunohistochemistry methods; it is also possible to detect viral DNA by polymerase chain reaction. At present, recurrent genital herpes is treated by the so-called episodic therapy or suppressor antiviral therapy, in the Czech Republic based on acyclovir or valacyclovir. Preventive measures are possible only to a limited extent, particular attention is paid to pregnant women and the risk of disseminated herpes infection in newborns. New preventive and therapeutic options continue to be developed: a preventive vaccine against HSV-2 has been successfully tested, but this is effective only in HSV-1 negative women; experimental therapeutic vaccination stimulating specific immunity has not yet been successful.

• MeSH
• antivirové látky terapeutické užití   MeSH
• herpes genitalis * diagnóza   farmakoterapie   prevence a kontrola   virologie   MeSH
• infekční komplikace v těhotenství diagnóza   prevence a kontrola   MeSH
• lidé MeSH
• lidský herpesvirus 1 izolace a purifikace   MeSH
• lidský herpesvirus 2 izolace a purifikace   MeSH
• sekundární prevence MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH

Seroepidemiological studies suggest that human herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are linked with several types of cancer; however, they do not appear to play a direct role and are considered to be cofactors. The abilities of HSV-1 and -2 to transform cells in vitro can be demonstrated by suppressing their lytic ability via irradiation with a specific dose of ultraviolet light, photoinactivation in the presence of photosensitizers (e.g., neutral red or methylene blue), and culture under specific conditions. Several mechanisms have been proposed to explain the actions of these viruses. According to the hit-and-run mechanism, viral DNA initiates transformation by interacting with cellular DNA and thereby inducing mutations and epigenetic changes, but is not involved in other stages of neoplastic progression. By contrast, according to the hijacking mechanism, viral products in infected cells can activate signaling pathways and thereby cause uncontrolled proliferation. Such products include RR1PK, an oncoprotein that activates the Ras pathway and is encoded by the HSV-2 gene ICP10. Virus-encoded microRNAs may act as cofactors in tumorigenesis of serous ovarian carcinoma and some prostate tumors. Herpes virus-associated growth factors that facilitate or suppress transformation may play important roles in tumor formation. Finally, there is much evidence that HSV-2 increases the risk of cervical cancer after infection of human papilloma viruses. Key words: HSV-1 - HSV-2 - cancer - mechanisms of transformation This work was supported by APVV 0621-12. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 11. 2016 Accepted: 20. 3. 2018.

• MeSH
• herpetické infekce komplikace   MeSH
• lidé MeSH
• lidský herpesvirus 1 * MeSH
• lidský herpesvirus 2 * MeSH
• nádory etiologie   MeSH
• virová transformace buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Treatment of infectious diseases remains one of the principal research target for many researchers and healthcare providers worldwide. Herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) are common human pathogens with an estimated 60-95% of the adult population infected by at least one of them. The worldwide disease burden of HSV is substantial, and acyclovir and related nucleoside analogues (viral DNA polymerase inhibitors) as therapies have led to significantly increased treatment efficacy of HSV infections. Although the treatment of HSV infection has greatly advanced through the use of nucleoside analogues therapy, the treatment efficacy has decreased significantly. This is due to the extensive use of nucleoside analogues drugs, which has created drug resistance, associated with other adverse effects as well. In this review, we aim to shed light on the HSV infection, the current pharmacologic treatment, and the use of dietary measures as alternative therapy option.Key words: HSV infection dietary measures antiviral drugs nucleoside analogues natural compounds.

• MeSH
• acyklovir terapeutické užití   MeSH
• antivirové látky terapeutické užití   MeSH
• herpes simplex dietoterapie   farmakoterapie   MeSH
• lidé MeSH
• lidský herpesvirus 1 MeSH
• lidský herpesvirus 2 MeSH
• nukleosidy analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• nukleosidy 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

Varicella-zoster virus (VZV), herpes simplex virus one (HSV-1) and herpes simplex virus two (HSV-2) represent three out of the eight known human herpesviruses and belong to the subfamily of α-herpesviruses. These viruses are present worldwide and humans are their sole host and reservoir. After the primary infection, these viruses persist in the body throughout life. The period of latency may be interrupted by reactivation of infection due to various factors. Each virus can induce a wide spectrum of diseases. The primary infection is typical for children and otherwise healthy individuals are often asymptomatic. It is mainly immunocompromised patients who are at risk of developing severe disease or complications when infected by these viruses. However, even in otherwise healthy individuals an infection by a-herpesviruses can run a severe course and lead to death.

• MeSH
• herpetické infekce epidemiologie   virologie   MeSH
• hostitel s imunodeficiencí MeSH
• lidé MeSH
• lidský herpesvirus 1 klasifikace   genetika   izolace a purifikace   MeSH
• lidský herpesvirus 2 klasifikace   genetika   izolace a purifikace   MeSH
• virus varicella zoster klasifikace   genetika   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH