Antiviral Activity of Resveratrol against Pseudorabies Virus
Received: 06-Sep-2022 / Manuscript No. jcidp-22-73853 / Editor assigned: 08-Sep-2022 / PreQC No. jcidp-22-73853 / Reviewed: 21-Sep-2022 / QC No. jcidp-22-73853 / Revised: 26-Sep-2022 / Manuscript No. jcidp-22-73853 / Published Date: 30-Sep-2022
Abstract
Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-𝜅𝛽 pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound
Introduction
Resveratrol (RSV) could be a present polyphenol stilbene found largely in hard grapes, mulberry, red wine, and peanuts. It’s obtainable within the Tran- and cis-isomer forms; but, the cis-resveratrol compound is unstable and simply remodeled into the trans-form once reacted to lightweight. It’s insoluble in water however soluble in polar solvents like grain alcohol and dimethyl sulfoxide [1]. Resveratrol scavenges for superoxide and hydroxyl radical in vitro, further as lipide hydroperoxyl radicals. Previous studies have shown resveratrol to boost longevity, regulate lipide levels, and act as a prophylactic compound against cancers and connected infective agent infections. It additionally attenuates superoxide generation within the mitochondria and inhibits mitochondrial pathology iatrogenic by arachidonic acid. The antiviral mechanisms and effects of RSV are wide studied in an exceedingly variety of viruses that embody grippe virus, hepatitis C virus, metabolism syncytial virus, pox herpes zoster virus, EBV, herpes simplex virus, human immunological disorder virus, African even-toed ungulate fever virus, picornavirus, human metapneumonia virus, and duck inflammation virus and in disseminated sclerosis, whose animal models will be iatrogenic by virus infection. In most of those studies, RSV showed outstanding recession of the virus infection with the exception of disseminated sclerosis and hepatitis C, wherever illness progression was worsened following administration of RSV [2].
Resveratrol (As Antiviral)
Resveratrol could be a naturally showing polyphenol (trans- 3,4,5-trihydroxystibene), principally sourced from grape skin and vino further as healthful plants e.g., Japanese knotweed, that has been used over a few years in several chronic diseases for its inhibitor, anti-inflammatory drug and anti-tumorigenic properties [3]. There’s growing proof that the oxidoreduction standing of cells plays a very important role in infective agent infections. RNA and deoxyribonucleic acid viruses will decrease glutathione levels and glutathione supplementation will inhibit infective agent replication. Resveratrol inhibits the grippe virus replication - it absolutely was thought that this was thanks to resveratrol’s influence on cellular oxidoreduction standing via glutathione. However, this inhibition was incontestible to not be directly associated to glutathione mediate inhibitor activity [4], however by inhibiting nuclear-cytoplasmic translocation of infective agent ribonucleoproteins and reducing the expression these days infective agent macromolecules related to the inhibition of protein enzyme C. Resveratrol derivatives are tested in vitro with some success on infective agent particle infectivity for the potential development of recent grippe treatments. Mixtures like resveratrol with N-acetylcysteine or glutathione, that have each inhibitor and antiviral effects, inhibits the proliferation of grippe virus and area unit of specific interest for serious influenza-associated complications.
Resveratrol has additionally been found to be a moderate substance of the N1L macromolecule that could be a virulence think about infective agent infections like variola. Moreover, resveratrol has been found to act synergistically with decitabine to inhibit human immunological disorder virus sort one (HIV-1) infectivity while not a corresponding increase in cellular toxicity. It additionally smothered drug-resistant HIV-1 strains with polymerase containing the M184V mutation.
It seems that resveratrol has repressive activity against numerous infective agent enzymes, AN example} it acts as an substance of ribonucleotide enzyme and antiretroviral natural action was represented between resveratrol and 5-azacytidine, a ribonucleoside analog, that is of significance in HIV-1 treatment. Resveratrol’s antiviral activity against the herpes simplex virus seems to be via a similar mechanism, particularly inhibition of ribonucleotide enzyme, impairing the expression of infective agent proteins to boot, a resveratrol tetramer additionally showed high efficiency as substance of the hepatitis C virus helicase [5]. Resveratrol additionally incontestable a potent repressive result on pseudorabies virus - a serious devastating illness within the even-toed ungulate business, thanks to its inhibition of nuclear issue letter of the alphabet B (NF-κB) activation and NF-κBdependent organic phenomenon via its repressive result on ikappaB (IκB) enzyme degradation.
Structure, Bioavailability, and performance
Resveratrol (RV), or 3,5,4 -trihydroxy-Trans-stilbene, could be a natural bioflavonoid compound found in plants and fruits. Its chemical structure is formed from 2 phenolic resin rings that area unit secure by a double vinyl resin bond, so forming the 3,5,4 - trihydroxystilbene with a relative molecular mass of 228.25 g/mol. Except for its natural isomers, cis- and transforms, many artificial and natural analogs of RSV exist, that exhibit similar or slightly variable medicine properties to RSV [6]. Resveratrol has poor water solubility and poor oral bioavailability and apace metabolized within the system. Its poor bioavailability is attributed to its speedy metabolism within the liver into glucuronides and sulfates. even supposing the quantity of oral dosing of RSV failed to considerably have an effect on its bioavailability in plasma, the kind of food consumed and intraindividual variations in metabolism were shown to considerably have an effect on its bioavailability in an exceedingly connected study, the plasma bioavailability of RSV halfhour once oral consumption of vino was solely in trace amounts, whereas moments later RSV glucuronides were systemically rife for a chronic time [7]. Recently, analysis has been targeted on developing structured nanoparticles that may enhance the bioavailability of RSV and prolong it’s unharness in vivo. Solid lipide nanoparticles (SLNs) Associate in Nursing nanostructured lipid carriers (NLCs) loaded with RSV were shown to own a demurrer potency of seventieth and stability lasting for over a pair of months. In vitro simulation studies showed a slow sustained unharness of RSV at each abdomen and enteric hydrogen ion concentration levels. Similarly, the utilization of zeinbased nanoparticles was reported to boost the in vivo delivery of RSV in mouse model of toxin shock [8].
Epstein - Barr virus
In Epstein-Barr virus (EBV) infection, RSV showed an enhanced inhibitory effect on EBV early antigen induction using Raji cells. It was also shown to reduce papilloma production in mouse by 60% after 20 weeks of inoculation. In another study, RSV was shown to dosedependently inhibit EBV lytic cycle by inhibition of transcription genes and proteins and diffused early antigen (EA-D), as well as inhibiting the activity of EBV immediate early protein: BRLF1 and BZLF1 promoters. This effect was seen to reduce virion production. Similarly, another in vitro study confirmed the previous finding that RSV does inhibit lytic gene expression and viral particle production in a dose-dependent manner [9]. Here its main antiviral mechanism was associated with inhibition of protein synthesis, reduction in ROS production, and inhibition of transcription factors NF-𝜅𝛽 and AP1. Since EBV is one of the most renowned oncogenic viruses, it is pertinent to study the role of EBV in cellular transformation and cancer progression. RSV was thus shown to prevent transformation of EBV in human B-cells through down regulation of antiapoptotic proteins: Mc1 and survivin. This was also linked to suppression of EBV induced signaling of NF-𝜅𝛽 and STAT-3, as well as miR-155 and miR34a in EBV infected cells.
Herpes Simplex Virus
RSV was shown to inhibit the replication of herpes simplex virus-1 and herpes simplex virus-2 (HSV-1 and HSV-2) in a dose-dependent and reversible way. In this study, the authors observed a reduction in virus yield as a result of inhibition of an early event in the replication cycle: decreased production of early viral protein ICP-4 [10]. RSV also delayed interphase stage of the cell cycle and prevented virus reactivation in neuron cells that were latently infected. In another study by the author using nude mice, topical application of 12.5% and 15% resveratrol ointment suppressed the development of cutaneous lesions in abraded skin infected with HSV-1. Similarly, application of 19% RSV cream on the vagina of mouse infected with HSV-2 and HSV-1 completely prevented the development of vaginal lesions, while the mortality rate was 3% as compared to the placebo group where mortality rate was 37%.These remarkable effects of RSV on HSV-1 and HSV-2 infections were reported to be due to the promotion of a rapid and sustained release of ROS, which resulted in the inhibition of NF-𝜅 𝛽 and extracellular signal-regulated kinases/mitogen activated protein kinases [11], as well as a blockade in the expression of immediate-early, early, and late HSV genes and viral DNA synthesis.
Respiratory Syncytial Virus
Respiratory syncytial virus (RPSV) infection is one of the most important viral diseases of the respiratory system affecting humans and it has no specific treatment. Administration of RSV in mice infected with RPSV reduced the accompanying inflammation and levels of interferon-gamma (IFN-𝛾). The mechanism here was attributed to control of toll-like receptor 3 expressions, inhibition of toll/IL-1R domain-containing adaptor inducing IFN (TRIF) signaling, and induction of muscarinic 2 receptor (M2R). In an in vitro study, RSV treatment in epithelial cells inoculated with RPSV resulted in decreased production of interleukin- (IL-) 6 and a partial reduction in viral replication. In a related study, RPSV infected mice treated with RSV also showed decreased levels of inflammatory cells and AHR. However, while RSV was able to drastically reduce the levels of nerve growth factor (NGF) after 21 days of infection, the level of brain derived neurotrophic factor (BDNF) was not significantly affected in both the treated and untreated groups [12]. Combination of RSV and baicalin (a flavonoid found in numerous species of Scutellaria) joint enema was shown to increase the levels of tumor necrosis factor-alpha (TNF-𝛼), IFN-𝛾, and IL-2 in mice infected with RPSV, which is believed to be among its antiviral mechanisms.
Hepatitis C Virus and Multiple Sclerosis
RSV was found to dosedependently enhance viral RNA replication in hepatitis C virus infection in vitro. Interestingly, RSV was also reported to reverse the antiviral effects of ribavirin and interferon on HCV RNA replication and was considered nontherapeutic in the treatment of HCV infection. Similarly, RSV was also found to exacerbate the clinical and histological signs of viral model of multiple sclerosis (MS), induced by Theiler’s murine encephalomyelitis virus (TMEV), which belongs to the Picornaviridae[13]. However, such studies are few and there are more studies highlighting the beneficial effects of RSV against viral infections, rather than its deleterious exacerbatory effects
Conclusion
Resveratrol has shown a high antiviral potential that can be explored in both human and animal viral infections. Its main antiviral mechanisms were seen to be elicited through inhibition of viral protein synthesis, inhibition of various transcription and signaling pathways, and inhibition of viral related gene expressions. Even though there are still limitations on its bioavailability following intake, which is being widely studied, more studies should be focused on its direct use in the amelioration of viral infections in humans and companion animals.
Conflict of Interest
The authors declare no conflict of interests.
Authors’ Contribution
All authors contributed equally to this work and have read and approved the final paper.
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Citation: Lucia S (2022) Antiviral Activity of Resveratrol against Pseudorabies Virus. J Clin Infect Dis Pract, 7: 160.
Copyright: © 2022 Lucia S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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