Repurposing chlorpromazine to treat COVID-19: The reCoVery study

Abstract

Objectives. -The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte-Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recentin vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity. Methods. -In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ + standard treatment).Conclusion. -This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects.

The Chemopreventive Potential of Diosmin and Hesperidin for COVID-19 and Its Comorbid Diseases

“…The approach through drug repurposing offers little hope, but still does not show the best results. However, the basic problem from repurposing the existing drugs is the raising of adverse effects in a long-term usage (Harrison, 2020 ;Plaze, et. al., 2020).…”

Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

“…Chlorpromazine, a dimethylamine derivative of phenothiazine used in the treatment of acute and chronic psychoses 4 , has been suggested as potential effective treatment for Covid-19 on the grounds of its antiviral and anti-inflammatory effects 5 . Specifically, several in-vitro studies [6][7][8] showed that chlorpromazine reduces viral replication of coronavirus-229E, MERS-CoV et SARS-CoV-1, possibly through the inhibition of clathrin-mediated endocytosis 9,10 .…”

“…Furthermore, several mouse models of sepsis [11][12][13][14] suggest that this medication is associated with a decrease in pro-inflammatory cytokines, including IL-2, IL4, IFN alpha, TNF, and GM-CSF, and an increase of the anti-inflammatory cytokine IL-10. Short-term use of chlorpromazine is generally well tolerated 5,15 , although side effects can occur, including QT interval prolongation, extrapyramidal symptoms, dry mouth, dizziness, urine retention, blurred vision, constipation, and hyperprolactinemia 5,15 .…”

The current landscape of coronavirus-host protein–protein interactions

“…Finally, we identified a dozen of host factors that are bound by coronavirus proteins and functionally modulated by compounds selected from antiviral screens, giving hints to explain the inhibition of coronavirus replication by these drugs. Among these molecules is chlorpromazine, an antipsychotic drug that is currently evaluated in a clinical trial against SARS-CoV-2 [78]. In conclusion, this work has highlighted the importance of several neglected coronavirus-host interactions that deserve to be further investigated.…”