Nejvíce citovaný článek - PubMed ID 32013134
Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development
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
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt's lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.
- Klíčová slova
- Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), anticancer properties, antiviral activities, cancer treatment, carcinogenesis, flavonoids, herpesviruses, molecular mechanisms, tumor viruses,
- MeSH
- anthokyaniny MeSH
- flavonoidy farmakologie terapeutické užití MeSH
- Herpesviridae * MeSH
- infekce virem Epsteina-Barrové * farmakoterapie MeSH
- Kaposiho sarkom * patologie MeSH
- karcinogeneze MeSH
- lidé MeSH
- lidský herpesvirus 8 * genetika MeSH
- nádory * farmakoterapie MeSH
- virus Epsteinův-Barrové genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- anthokyaniny MeSH
- flavonoidy MeSH
Herpesviruses are one of the most contagious DNA viruses that threaten human health, causing severe diseases, including, but not limited to, certain types of cancer and neurological complications. The overuse and misuse of anti-herpesvirus drugs are key factors leading to drug resistance. Therefore, targeting human herpesviruses with natural products is an attractive form of therapy, as it might improve treatment efficacy in therapy-resistant herpesviruses. Plant polyphenols are major players in the health arena as they possess diverse bioactivities. Hence, in this article, we comprehensively summarize the recent advances that have been attained in employing plant non-flavonoid polyphenols, such as phenolic acids, tannins and their derivatives, stilbenes and their derivatives, lignans, neolignans, xanthones, anthraquinones and their derivatives, curcuminoids, coumarins, furanocoumarins, and other polyphenols (phloroglucinol) as promising anti-herpesvirus drugs against various types of herpesvirus such as alpha-herpesviruses (herpes simplex virus type 1 and 2 and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus). The molecular mechanisms of non-flavonoid polyphenols against the reviewed herpesviruses are also documented.
- Klíčová slova
- Epstein–Barr virus (EBV), HSV-1, HSV-2, Kaposi sarcoma-associated herpesvirus (KSHV), antiviral activity, herpes simplex virus, human cytomegalovirus (HCMV), natural products, non-flavonoid polyphenols, polyphenols, varicella-zoster virus (VZV),
- MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- herpetické infekce * farmakoterapie MeSH
- infekce virem Epsteina-Barrové * farmakoterapie MeSH
- lidé MeSH
- polyfenoly farmakologie terapeutické užití MeSH
- virus Epsteinův-Barrové MeSH
- virus varicella zoster MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antivirové látky MeSH
- polyfenoly 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
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
The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue "Recent Advances in Herpesviruses Research: What's in the Pipeline?" aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.
- Klíčová slova
- COVID-19, SARS-CoV-2, alkaloids, anti-herpesvirus drugs, herpesviruses,
- MeSH
- alkaloidy farmakologie MeSH
- antivirové látky farmakologie MeSH
- Betacoronavirus účinky léků MeSH
- COVID-19 MeSH
- Herpesviridae účinky léků MeSH
- herpetické infekce farmakoterapie MeSH
- koronavirové infekce farmakoterapie MeSH
- lidé MeSH
- pandemie MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- SARS-CoV-2 MeSH
- virová pneumonie farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- úvodníky MeSH
- Názvy látek
- alkaloidy MeSH
- antivirové látky MeSH
- rostlinné extrakty MeSH