Intracellular redox-modulated pathways as targets for effective approaches in the treatment of viral infection

Alessandra Fraternale, Carolina Zara, Marta De Angelis, Lucia Nencioni, Anna Teresa Palamara, Michele Retini, Tomas Di Mambro, Mauro Magnani, Rita Crinelli

Research output: Contribution to journalReview articlepeer-review

Abstract

Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses.

Original languageEnglish
Article number3603
JournalInternational Journal of Molecular Sciences
Volume22
Issue number7
DOIs
Publication statusPublished - Apr 1 2021

Keywords

  • Anti-inflammatory
  • Antiviral
  • Glutathione (GSH)
  • Pro-GSH molecules
  • Redox signaling
  • Viral infection

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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