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

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

• Klíčová slova
• Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, berberine, cancer, herpes simplex virus, human cytomegalovirus, inflammation, oncogenic herpesviruses,
• MeSH
• antivirové látky terapeutické užití   MeSH
• berberin terapeutické užití   MeSH
• Herpesviridae klasifikace   účinky léků   patogenita   MeSH
• herpetické infekce komplikace   farmakoterapie   MeSH
• karcinogeneze účinky léků   MeSH
• klinické zkoušky jako téma MeSH
• latence viru účinky léků   MeSH
• lidé MeSH
• myši MeSH
• nádory farmakoterapie   virologie   MeSH
• replikace viru účinky léků   MeSH
• zánět farmakoterapie   virologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH
• berberin MeSH

Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

• Klíčová slova
• Curcuma longa L., curcumin, herpesviruses, inflammation, mechanisms and pathways, phenolics, viral infections,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are still many activities yet to be studied. In this work, brassicasterol exerts a therapeutic utility in an in vitro setting against herpes simplex virus type 1 (HSV-1) and Mycobacterium tuberculosis (Mtb) as well as a considerable inhibitory property against human angiotensin-converting enzyme (ACE) that plays a dynamic role in regulating blood pressure. The antireplicative effect of brassicasterol against HSV-1 is remarkably detected (50% inhibitory concentration (IC50): 1.2 µM; selectivity index (SI): 41.7), while the potency of its effect is ameliorated through the combination with standard acyclovir with proper SI (IC50: 0.7 µM; SI: 71.4). Moreover, the capacity of this compound to induce an adequate level of antituberculosis activity against all Mtb strains examined (minimum inhibitory concentration values ranging from 1.9 to 2.4 µM) is revealed. The anti-ACE effect (12.3 µg/mL; 91.2% inhibition) is also ascertained. Molecular docking analyses propose that the mechanisms by which brassicasterol induces anti-HSV-1 and anti-Mtb might be related to inhibiting vital enzymes involved in HSV-1 replication and Mtb cell wall biosynthesis. In summary, the obtained results suggest that brassicasterol might be promising for future anti-HSV-1, antituberculosis, and anti-ACE drug design.

• Klíčová slova
• ACE, HSV, HSV-1 DNA polymerase, HSV-1 TK, Mycobacterium tuberculosis, UDP-galactopyranose mutase, brassicasterol, human CDK2, phytosterols,
• Publikační typ
• časopisecké články 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