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.
Highlights
Pulmonary Delivery of Fenretinide in COVID-19 In COVID-19 patients, the rapid evolution of the disease requires prompt treatment because only a narrow time window exists for therapeutic intervention
The decrease of TNF-α [25,26] and the antiangiogenic effect [97,98] provided by fenretinide, added to the same effects provided by thalidomide and lenalidomide, should boost the anti-inflammatory response elicited by the combination
There is no direct evidence of fenretinide application in COVID-19, the multiple inhibition mechanisms demonstrated in the studied viruses and the involvement of fenretinide in multiple pathways controlling viral replication strongly suggest that fenretinide could provide an indirect antiviral activity towards SARS-CoV-2, as well as other virus types, by means of the induction of an “antiviral environment” hindering infection
Summary
In SARS-CoV-2 infection, the early onset of a rapid viral replication may cause extensive apoptosis of epithelial and endothelial cells and vascular leakage. This frequently leads to acute lung injury and lethal inflammatory responses [4]. Due to its poly-pharmacology, fenretinide administration by pulmonary formulations may be expected to be protective against acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) caused by SARS-CoV infection and could represent a useful tool in a multimodal therapy aimed at establishing a rapid anti-inflammatory and antiviral effect
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
