Anti-herpesvirus Drugs and Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 52235

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Special Issue Editor


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Guest Editor
Director, Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USA
Interests: molecular virology; antiviral therapy; herpesvirus; human cytomegalovirus; anti-herpetic drugs

Special Issue Information

Dear Colleagues,

Since the advent of trifluridine and idoxuridine, the antimicrobial community has been looking for better, more specific drugs and vaccines to both prevent and suppress infections of herpesviruses. The greatest active pharmaceutical ingredient since then has been acyclovir and its derivatives; the greatest vaccine successes against a human herpesvirus have been against varicella zoster virus. However, antiherpetic drug and vaccine discovery continues today, especially with the more recent clinical licensing of drugs such as letermovir and animamevir and vaccines such as Shingrix.

This Special Issue takes a look at both current antiherpetic interventions available today, with medications and vaccines used to act prophylactically and therapeutically, and where the field is moving in the near future. We also explore newer ideas for long-term suppression and perhaps even removal of latent virus.

Prof. Dr. Barry J. Margulies
Guest Editor

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Keywords

  • antiviral chemotherapy
  • acyclovir
  • aciclovir
  • ganciclovir
  • valtrex
  • antiherpetic
  • varivax
  • zostavax
  • oka
  • herpes vaccine
  • Marek’s Disease Virus
  • veterinary herpes
  • rhinopneumonitis
  • pneumabort-K
  • cytovene
  • letermovir
  • maribavir
  • amenalief

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Published Papers (12 papers)

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Editorial

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2 pages, 179 KiB  
Editorial
The World of Antiherpetic Vaccines and Drugs, 2022
by Barry J. Margulies
Viruses 2022, 14(5), 850; https://doi.org/10.3390/v14050850 - 20 Apr 2022
Viewed by 1567
Abstract
The world of antiherpetics has grown by leaps and bounds since the discovery of what would become the first antiherpetic drug in 1964 [...] Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)

Research

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18 pages, 1687 KiB  
Article
Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model
by K. Yeon Choi, Nadia S. El-Hamdi and Alistair McGregor
Viruses 2022, 14(4), 760; https://doi.org/10.3390/v14040760 - 6 Apr 2022
Cited by 5 | Viewed by 2377
Abstract
Congenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) [...] Read more.
Congenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) vaccine strategy demonstrated complete protection against congenital GPCMV (22122 strain) and required neutralizing antibodies to various viral glycoprotein complexes. This included gB, essential for all cell types, and the pentamer complex (PC) for infection of non-fibroblast cells. All GPCMV research has utilized prototype strain 22122 limiting the translational impact, as numerous human CMV strains exist allowing re-infection and congenital CMV despite convalescent immunity. A novel GPCMV strain isolate (designated TAMYC) enabled vaccine cross strain protection studies. A GPCMV DISC (PC+) vaccine (22122 strain) induced a comprehensive immune response in animals, but vaccinated animals challenged with the TAMYC strain virus resulted in sustained viremia and the virus spread to target organs (liver, lung and spleen) with a significant viral load in the salivary glands. Protection was better than natural convalescent immunity, but the results fell short of previous DISC vaccine sterilizing immunity against the homologous 22122 virus challenge, despite a similarity in viral glycoprotein sequences between strains. The outcome suggests a limitation of the current DISC vaccine design against heterologous infection. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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12 pages, 1152 KiB  
Article
Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine
by Lauren M. Hook, Sita Awasthi, Tina M. Cairns, Mohamad-Gabriel Alameh, Bernard T. Fowler, Kevin P. Egan, Molly M. H. Sung, Drew Weissman, Gary H. Cohen and Harvey M. Friedman
Viruses 2022, 14(3), 540; https://doi.org/10.3390/v14030540 - 5 Mar 2022
Cited by 8 | Viewed by 3135
Abstract
The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine [...] Read more.
The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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15 pages, 4652 KiB  
Article
The Synthesis and Anti-Cytomegalovirus Activity of Piperidine-4-Carboxamides
by Xin Guo, Ayan Kumar Ghosh, Robert F. Keyes, Francis Peterson, Michael Forman, David J. Meyers and Ravit Arav-Boger
Viruses 2022, 14(2), 234; https://doi.org/10.3390/v14020234 - 25 Jan 2022
Cited by 2 | Viewed by 3019
Abstract
Treatment options for human cytomegalovirus (CMV) remain limited and are associated with significant adverse effects and the selection of resistant CMV strains in transplant recipients and congenitally infected infants. Although most approved drugs target and inhibit the CMV DNA polymerase, additional agents with [...] Read more.
Treatment options for human cytomegalovirus (CMV) remain limited and are associated with significant adverse effects and the selection of resistant CMV strains in transplant recipients and congenitally infected infants. Although most approved drugs target and inhibit the CMV DNA polymerase, additional agents with distinct mechanisms of action are needed for the treatment and prevention of CMV. In a large high throughput screen using our CMV-luciferase reporter Towne, we identified several unique inhibitors of CMV replication. Here, we synthesize and test in vitro 13 analogs of the original NCGC2955 hit (1). Analogs with no activity against the CMV-luciferase at 10 µM and 30 µM (26, 1014) were removed from further analysis. Three analogs (79) inhibited CMV replication in infected human foreskin fibroblasts. The EC50 of (1) was 1.7 ± 0.6 µM and 1.99 ± 0.15 µM, based on luciferase and plaque assay, respectively. Compounds 7, 8, and 9 showed similar activities: the EC50 values of 7 were 0.21 ± 0.06 µM (luciferase) and 0.55 ± 0.06 (plaque), of 8: 0.28 ± 0.06 µM and 0.42 ± 0.07, and of 9: 0.30 ± 0.05 µM (luciferase) and 0.35 ± 0.07 (plaque). The CC50 for 7, 8, and 9 in non-infected human foreskin fibroblasts was > 500µM, yielding a selectivity index of >1500. Compounds 1, 7, and 8 were also tested in CMV-infected primary human hepatocytes and showed a dose–response against CMV by luciferase activity and viral protein expression. None of the active compounds inhibited herpes simplex virus 1 or 2. Compounds 7 and 8 inhibited mouse CMV replication in vitro. Both inhibited CMV at late stages of replication; 7 reduced virus yield at all late time points, although not to the same degree as letermovir. Finally, the activity of analog 8 was additive with newly identified CMV inhibitors (MLS8969, NFU1827, MSL8554, and MSL8091) and with ganciclovir. Further structural activity development should provide promising anti-CMV agents for use in clinical studies. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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12 pages, 1685 KiB  
Article
Peptide Inhibitor of Complement C1, RLS-0071, Reduces Zosteriform Spread of Herpes Simplex Virus Type 1 Skin Infection and Promotes Survival in Infected Mice
by Maimoona S. Bhutta, Daniel G. Sausen, Kirstin M. Reed, Elisa S. Gallo, Pamela S. Hair, Brittany P. Lassiter, Neel K. Krishna, Kenji M. Cunnion and Ronen Borenstein
Viruses 2021, 13(8), 1422; https://doi.org/10.3390/v13081422 - 22 Jul 2021
Cited by 3 | Viewed by 4233
Abstract
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen primarily transmitted through skin-to-skin contact, especially on and around mucosal surfaces where there is contact with contaminated saliva during periods of viral shedding. It is estimated that 90% of adults worldwide have [...] Read more.
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen primarily transmitted through skin-to-skin contact, especially on and around mucosal surfaces where there is contact with contaminated saliva during periods of viral shedding. It is estimated that 90% of adults worldwide have HSV-1 antibodies. Cutaneous HSV-1 infections are characterized by a sensation of tingling or numbness at the initial infection site followed by an eruption of vesicles and then painful ulcers with crusting. These symptoms can take ten days to several weeks to heal, leading to significant morbidity. Histologically, infections cause ballooning degeneration of keratinocytes and formation of multinucleated giant cells, ultimately resulting in a localized immune response. Commonly prescribed treatments against HSV-1 infections are nucleoside analogs, such as acyclovir (ACV). However, the emergence of ACV-resistant HSV (ACVR-HSV) clinical isolates has created an urgent need for the development of compounds to control symptoms of cutaneous infections. RLS-0071, also known as peptide inhibitor of complement C1 (PIC1), is a 15-amino-acid anti-inflammatory peptide that inhibits classical complement pathway activation and modulates neutrophil activation. It has been previously shown to aid in the healing of chronic diabetic wounds by inhibiting the excessive activation of complement component C1 and infiltration of leukocytes. Here, we report that treatment of cutaneous infections of HSV-1 and ACVR-HSV-1 in BALB/cJ mice with RLS-0071 significantly reduced the rate of mortality, decreased zosteriform spread, and enhanced the healing of the infection-associated lesions compared to control-treated animals. Therefore, RLS-0071 may work synergistically with other antiviral drugs to aid in wound healing of HSV-1 cutaneous infection and may potentially aid in rapid wound healing of other pathology not limited to HSV-1. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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11 pages, 1695 KiB  
Article
Antibodies Elicited in Response to a Single Cycle Glycoprotein D Deletion Viral Vaccine Candidate Bind C1q and Activate Complement Mediated Neutralization and Cytolysis
by Maria Luisa Visciano, Aakash Mahant Mahant, Carl Pierce, Richard Hunte and Betsy C. Herold
Viruses 2021, 13(7), 1284; https://doi.org/10.3390/v13071284 - 30 Jun 2021
Cited by 6 | Viewed by 2989
Abstract
Herpes simplex virus (HSV) prevention is a global health priority but, despite decades of research, there is no effective vaccine. Prior efforts focused on generating glycoprotein D (gD) neutralizing antibodies, but clinical trial outcomes were disappointing. The deletion of gD yields a single-cycle [...] Read more.
Herpes simplex virus (HSV) prevention is a global health priority but, despite decades of research, there is no effective vaccine. Prior efforts focused on generating glycoprotein D (gD) neutralizing antibodies, but clinical trial outcomes were disappointing. The deletion of gD yields a single-cycle candidate vaccine (∆gD-2) that elicits high titer polyantigenic non-gD antibodies that exhibit little complement-independent neutralization but mediate antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Active or passive immunization with ΔgD-2 completely protects mice from lethal disease and latency following challenge with clinical isolates of either serotype. The current studies evaluated the role of complement in vaccine-elicited protection. The immune serum from the ΔgD-2 vaccinated mice exhibited significantly greater C1q binding compared to the serum from the gD protein vaccinated mice with infected cell lysates from either serotype as capture antigens. The C1q-binding antibodies recognized glycoprotein B. This resulted in significantly greater antibody-mediated complement-dependent cytolysis and neutralization. Notably, complete protection was preserved when the ΔgD-2 immune serum was passively transferred into C1q knockout mice, suggesting that ADCC and ADCP are sufficient in mice. We speculate that the polyfunctional responses elicited by ΔgD-2 may prove more effective in preventing HSV, compared to the more restrictive responses elicited by adjuvanted gD protein vaccines. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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13 pages, 2935 KiB  
Article
Arsenicals, the Integrated Stress Response, and Epstein–Barr Virus Lytic Gene Expression
by Jaeyeun Lee, Jennifer Stone, Prashant Desai, John G. Kosowicz, Jun O. Liu and Richard F. Ambinder
Viruses 2021, 13(5), 812; https://doi.org/10.3390/v13050812 - 30 Apr 2021
Cited by 6 | Viewed by 2924
Abstract
Following our observation that clofoctol led to Epstein–Barr virus (EBV) lytic gene expression upon activation of the integrated stress response (ISR), we decided to investigate the impact of As2O3 on viral lytic gene expression. As2O3 has also [...] Read more.
Following our observation that clofoctol led to Epstein–Barr virus (EBV) lytic gene expression upon activation of the integrated stress response (ISR), we decided to investigate the impact of As2O3 on viral lytic gene expression. As2O3 has also been reported to activate the ISR pathway by its activation of the heme-regulated inhibitor (HRI). Our investigations show that As2O3 treatment leads to eIF2α phosphorylation, upregulation of ATF4 and TRB3 expression, and an increase of EBV Zta gene expression in lymphoid tumor cell lines as well as in naturally infected epithelial cancer cell lines. However, late lytic gene expression and virion production were blocked after arsenic treatment. In comparison, a small molecule HRI activator also led to increased Zta expression but did not block late lytic gene expression, suggesting that As2O3 effects on EBV gene expression are also mediated through other pathways. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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Review

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17 pages, 368 KiB  
Review
Recent Advances in Developing Treatments of Kaposi’s Sarcoma Herpesvirus-Related Diseases
by Eleonora Naimo, Jasmin Zischke and Thomas F. Schulz
Viruses 2021, 13(9), 1797; https://doi.org/10.3390/v13091797 - 9 Sep 2021
Cited by 19 | Viewed by 4099
Abstract
Kaposi-sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is the causative agent of several malignancies, including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). Active KSHV replication has also been associated with a pathological condition called KSHV inflammatory cytokine [...] Read more.
Kaposi-sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is the causative agent of several malignancies, including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). Active KSHV replication has also been associated with a pathological condition called KSHV inflammatory cytokine syndrome (KICS), and KSHV may play a role in rare cases of post-transplant polyclonal lymphoproliferative disorders. Several commonly used herpesviral DNA polymerase inhibitors are active against KSHV in tissue culture. Unfortunately, they are not always efficacious against KSHV-induced diseases. To improve the outcome for the patients, new therapeutics need to be developed, including treatment strategies that target either viral proteins or cellular pathways involved in tumor growth and/or supporting the viral life cycle. In this review, we summarize the most commonly established treatments against KSHV-related diseases and review recent developments and promising new compounds that are currently under investigation or on the way to clinical use. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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14 pages, 291 KiB  
Review
Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses
by Brent A. Stanfield, Konstantin G. Kousoulas, Agustin Fernandez and Edward Gershburg
Viruses 2021, 13(8), 1637; https://doi.org/10.3390/v13081637 - 18 Aug 2021
Cited by 17 | Viewed by 4462
Abstract
Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently [...] Read more.
Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
21 pages, 3695 KiB  
Review
Amenamevir, a Helicase-Primase Inhibitor, for the Optimal Treatment of Herpes Zoster
by Kimiyasu Shiraki, Shinichiro Yasumoto, Nozomu Toyama and Hiroaki Fukuda
Viruses 2021, 13(8), 1547; https://doi.org/10.3390/v13081547 - 5 Aug 2021
Cited by 38 | Viewed by 9414
Abstract
Acyclovir, valacyclovir, and famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Helicase-primase inhibitors (HPIs) inhibit replication fork progression that separates double DNA strands into two single strands during DNA synthesis. The HPIs amenamevir and pritelivir [...] Read more.
Acyclovir, valacyclovir, and famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Helicase-primase inhibitors (HPIs) inhibit replication fork progression that separates double DNA strands into two single strands during DNA synthesis. The HPIs amenamevir and pritelivir have novel mechanisms of anti-herpetic action, and their once-daily administration has clinical efficacy for genital herpes. Among HPIs, amenamevir has anti-VZV activity. The concentrations of HSV-1 and VZV required for the 50% plaque reduction of amenamevir were 0.036 and 0.047 μM, respectively. We characterized the features of amenamevir regarding its mechanism, resistance, and synergism with acyclovir. Its antiviral activity was not influenced by the viral replication cycle, in contrast to acyclovir. A clinical trial of amenamevir for herpes zoster demonstrated its non-inferiority to valacyclovir. To date, amenamevir has been successfully used in over 1,240,000 patients with herpes zoster in Japan. Post-marketing surveillance of amenamevir in Japan reported side effects with significant potential risk identified by the Japanese Risk Management Plan, including thrombocytopenia, gingival bleeding, and palpitations, although none of these were serious. The clinical efficacy and safety profiles of amenamevir were established in patients with herpes zoster. Therefore, amenamevir as an HPI opens a new era of anti-herpes therapy. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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18 pages, 1653 KiB  
Review
Antiviral Active Compounds Derived from Natural Sources against Herpes Simplex Viruses
by Lukas van de Sand, Maren Bormann, Yasmin Schmitz, Christiane Silke Heilingloh, Oliver Witzke and Adalbert Krawczyk
Viruses 2021, 13(7), 1386; https://doi.org/10.3390/v13071386 - 16 Jul 2021
Cited by 37 | Viewed by 5000
Abstract
Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence [...] Read more.
Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence of resistance to conventional antiviral drugs make the therapy of such infections even more challenging. For instance, the frequent and long-term use of acyclovir and other nucleoside analogues targeting the viral DNA-polymerase enhance the development of resistant viruses. Particularly, the incidental increase of those strains in immunocompromised patients is alarming and represent a major health concern. Alternative treatment concepts are clearly needed. Natural products such as herbal medicines showed antiherpetic activity in vitro and in vivo and proved to be an excellent source for the discovery and isolation of novel antivirals. By this means, numerous plant-derived compounds with antiviral or antimicrobial activity could be isolated. Natural medicines and their ingredients are well-tolerated and could be a good alternative for treating herpes simplex virus infections. This review provides an overview of the recent status of natural sources such as plants, bacteria, fungi, and their ingredients with antiviral activity against herpes simplex viruses. Furthermore, we highlight the most potent herbal medicines and ingredients as promising candidates for clinical investigation and give an overview about the most important drug classes along with their potential antiviral mechanisms. The content of this review is based on articles that were published between 1996 and 2021. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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12 pages, 1573 KiB  
Review
Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2
by Lauren A. Sadowski, Rista Upadhyay, Zachary W. Greeley and Barry J. Margulies
Viruses 2021, 13(7), 1228; https://doi.org/10.3390/v13071228 - 25 Jun 2021
Cited by 64 | Viewed by 6699
Abstract
Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaherpesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that [...] Read more.
Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaherpesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that we provide interventions to keep them at bay, especially in immunocompromised patients. While numerous experimental vaccines are under consideration, current intervention consists solely of antiviral chemotherapeutic agents. This review explores all of the clinically approved drugs used to prevent the worst sequelae of recurrent outbreaks by these viruses. Full article
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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