Repurposing Psychotropic Agents for Viral Disorders: Beyond Covid

Abstract

Recent reports have highlighted the possible role of the antipsychotic chlorpromazine and the antidepressant fluvoxamine as anti-coronavirus disease 2019 (COVID-19) agents. The objective of this narrative review is to explore what is known about the activity of psychotropic medications against viruses in addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PubMed was queried for ''drug repurposing, antiviral activity,'' and for ''antiviral activity'' with ''psychotropic drugs'' and individual agents, through November 2020. Of more than 100 psychotropic agents, 37 drugs, including 27 with a history of pediatric use were identified, which had been studied in the preclinical setting and found to have activity against viruses which are human pathogens. Effects were evaluated by type of virus and by category of psychotropic agent. Activity was identified both against viruses known to cause epidemics such as SARS-CoV-2 and Ebola and against those that are the cause of rare disorders such as Human Papillomatosis Virus-related respiratory papillomatosis. Individual drugs and classes of psychotropics often had activity against multiple viruses, with promiscuity explained by shared viral or cellular targets. Safety profiles of psychotropics may be more tolerable in this context than when they are used long-term in the setting of psychiatric illness. Nonetheless, translation of in vitro results to the clinical arena has been slow. Psychotropic medications as a class deserve further study, including in clinical trials for repurposing as antiviral drugs for children and adults.

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis

“…Fluoxetine and other SSRIs might have a direct anti-viral effect [ 25 , 26 ]. Interestingly, it has been found that the COVID-19 virus activates the ceramide system that then facilitates viral entry into cells [ 27 ].…”

Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors

“… 56 Other drugs from this family were also shown to suppress pathogenic polyomaviruses. 57 Indeed, our experiments indicated that the R92 pocket can accommodate trifluoperazine (TFP) which is chemically closely related to chlorpromazine. When BKVP1.26-299 crystals were soaked with TFP, rapid cracking and dissolution of the crystals was observed at compound concentrations above 1 mM.…”

“…5 and 4D ). Our discovery of a direct interaction between polyomavirus VP1 and TFP is unexpected, given the currently assumed function of this drug as endocytosis inhibitor, 57 and calls for further investigation of its action mechanism. Alongside with the smaller fragments, the TFP molecule can provide a further starting point for rational inhibitor design.…”

Role of Lipid Rafts in Pathogen-Host Interaction - A Mini Review

“…Similarly, anesthetic drugs such as propofol, halothane and barbiturates were found to block virus entry due to their interaction with lipid rafts ( 84 , 120 ). Antidepressants act by displacing G protein responsible for increasing cAMP (Gα s ) from lipid rafts, and drugs such as fluvoxamine, and fluoxetine are known to block the entry of viruses ( 102 , 116 – 118 , 147 , 149 ). Taken together, repurposing these existing drugs against newly emerging pathogenic virus may provide a good strategy since they have a proven safety record and can be deployed in a short time to treat viral infections.…”

“…Furthermore, several pharmaceutical drugs used in treatment of other disorders were found to interact with lipid rafts resulting in blocking the entry of pathogens into the cells. Some of the well-known drugs targeting lipid rafts are statins (144,145), anesthetics (146), and psychotropic drugs (147)(148)(149)(150). Several statins such as lovastatin, mevastatin, fluvastatin, simvastatin, atorvastatin and nystatin used for the treatment of cardiovascular disease were reported to block virus entry into cells (64,65,72,101,107,109,110,113,122).…”