Article

GSH and analogs in antiviral therapy.

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, PU, Italy.
Molecular Aspects of Medicine (Impact Factor: 10.3). 10/2008; 30(1-2):99-110. DOI: 10.1016/j.mam.2008.09.001
Source: PubMed

ABSTRACT Reduced glutathione (GSH) is the most prevalent non-protein thiol in animal cells. Its de novo and salvage synthesis serves to maintain a reduced cellular environment. GSH is the most powerful intracellular antioxidant and plays a role in the detoxification of a variety of electrophilic compounds and peroxides via catalysis by glutathione-S-transferases (GST) and glutathione peroxidases (GPx). As a consequence, the ratio of reduced and oxidized glutathione (GSH:GSSG) serves as a representative marker of the antioxidative capacity of the cell. A deficiency in GSH puts the cell at risk for oxidative damage. An imbalance in GSH is observed in a wide range of pathologies, such as cancer, neurodegenerative diseases, cystic fibrosis (CF), several viral infections including HIV-1, as well as in aging. Several reports have provided evidence for the use of GSH and molecules able to replenish intracellular GSH levels in antiviral therapy. This non-conventional role of GSH and its analogs as antiviral drugs is discussed in this chapter.

Full-text

Available from: Alessandra Fraternale, Aug 28, 2014
3 Followers
 · 
154 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza virus infections represent a big issue for public health since effective treatments are still lacking. In fact, the efficacy of anti-influenza agents is limited by the rapid occurrence of drug resistance. Thus, many efforts have been devoted to identify new therapeutic strategies targeting the virus-host cell interactions. Oxidative stress is a characteristic of some viral infections including influenza. Because antioxidants protect cells from damage caused by reactive oxygen species induced by different stimuli including pathogens, they represent interesting molecules to fight infectious diseases. However, most of the available studies have found that these would-be panaceas could actually exacerbate the diseases they claim to prevent, and have thus revealed "the dark side" of these molecules. This review article discusses the latest opportunities and drawbacks of the antioxidants used in anti-influenza therapy and new perspectives.
    Current Topics in Medicinal Chemistry 12/2014; 14(22). DOI:10.2174/1568026614666141203125211 · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Reactive oxygen species (ROS) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. Low levels of ROS are involved in cellular signaling and are well controlled by the cellular antioxidant defense system. Elevated levels of ROS generation due to pollutants, toxins and radiation exposure, as well as infections, are associated with oxidative stress causing cellular damage. Several respiratory viruses, including respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza, induce increased ROS formation, both intracellularly and as a result of increased inflammatory cell recruitment at the site of infection. They also reduce antioxidant enzyme (AOE) levels and/or activity, leading to unbalanced oxidative-antioxidant status and subsequent oxidative cell damage. Expression of several AOE is controlled by the activation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2), through binding to the antioxidant responsive element (ARE) present in the AOE gene promoters. While exposure to several pro-oxidant stimuli usually leads to Nrf2 activation and upregulation of AOE expression, respiratory viral infections are associated with inhibition of AOE expression/activity, which in the case of RSV and hMPV is associated with reduced Nrf2 nuclear localization, decreased cellular levels and reduced ARE-dependent gene transcription. Therefore, administration of antioxidant mimetics or Nrf2 inducers represents potential viable therapeutic approaches to viral-induced diseases, such as respiratory infections and other infections associated with decreased cellular antioxidant capacity.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Copyright: © 2014 Komaravelli N, et al. 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.