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Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment In COVID-19

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2020 May 31
PMID 32471278
Citations 14
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Abstract

At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.

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References
1.
Gagliostro V, Casas J, Caretti A, Abad J, Tagliavacca L, Ghidoni R . Dihydroceramide delays cell cycle G1/S transition via activation of ER stress and induction of autophagy. Int J Biochem Cell Biol. 2012; 44(12):2135-43. DOI: 10.1016/j.biocel.2012.08.025. View

2.
Gassen N, Niemeyer D, Muth D, Corman V, Martinelli S, Gassen A . SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat Commun. 2019; 10(1):5770. PMC: 6920372. DOI: 10.1038/s41467-019-13659-4. View

3.
Makena M, Koneru B, Nguyen T, Kang M, Reynolds C . Reactive Oxygen Species-Mediated Synergism of Fenretinide and Romidepsin in Preclinical Models of T-cell Lymphoid Malignancies. Mol Cancer Ther. 2017; 16(4):649-661. DOI: 10.1158/1535-7163.MCT-16-0749. View

4.
Fazi B, Bursch W, Fimia G, Nardacci R, Piacentini M, Di Sano F . Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy. 2008; 4(4):435-41. DOI: 10.4161/auto.5669. View

5.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. PMC: 7159299. DOI: 10.1016/S0140-6736(20)30183-5. View