TY - JOUR
T1 - Intracellular redox-modulated pathways as targets for effective approaches in the treatment of viral infection
AU - Fraternale, Alessandra
AU - Zara, Carolina
AU - De Angelis, Marta
AU - Nencioni, Lucia
AU - Palamara, Anna Teresa
AU - Retini, Michele
AU - Di Mambro, Tomas
AU - Magnani, Mauro
AU - Crinelli, Rita
N1 - Funding Information:
This work was partially supported by: University of Urbino Carlo Bo (M.M., A.F. grants); the Italian Ministry of Instruction, Universities and Research?MIUR PRIN 2017 2017BMK8JR006 (project ?ORIGINALE CHEMIAE in Antiviral Strategy?Origin and Modernization of Multi-Compo-nent Chemistry as a Source of Innovative Broad Spectrum Antiviral Strategy?) (L.N.); MIUR PONARS 01_00597_OR4 (A.T.P.) grants, Fondazione Cenci Bolognetti Istituto Pasteur Italia (L.N.) grants and Ateneo grants (LN).
Funding Information:
Funding: This work was partially supported by: University of Urbino Carlo Bo (M.M., A.F. grants); the Italian Ministry of Instruction, Universities and Research—MIUR PRIN 2017 2017BMK8JR006 (project “ORIGINALE CHEMIAE in Antiviral Strategy—Origin and Modernization of Multi-Component Chemistry as a Source of Innovative Broad Spectrum Antiviral Strategy”) (L.N.); MIUR PONARS 01_00597_OR4 (A.T.P.) grants, Fondazione Cenci Bolognetti Istituto Pasteur Italia (L.N.) grants and Ateneo grants (LN).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Anti-inflammatory
KW - Antiviral
KW - Glutathione (GSH)
KW - Pro-GSH molecules
KW - Redox signaling
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=85103158012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103158012&partnerID=8YFLogxK
U2 - 10.3390/ijms22073603
DO - 10.3390/ijms22073603
M3 - Review article
C2 - 33808471
AN - SCOPUS:85103158012
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 7
M1 - 3603
ER -