Antiviral Potency of Antipsychotics: A New Therapeutic Strength

The rationale behind alternative medicine is to repurpose existing medicines to meet unmet medical needs. Antipsychotics, originally developed to treat mental disorders such as schizophrenia and bipolar disorder, are now being evaluated for broader therapeutic potential. From safety data and known mechanisms of action, scientists are testing the effects of antipsychotics (APs) on viruses as a consequence to the lack of successful antivirals available. For example, some APs inhibit viral replication, prevent viral entry into host cells, or modulate immune responses. However, pre-experimental and clinical studies are needed to validate these findings. Drug repurposing has been a promising strategy, specifically after the devastating COVID-19 pandemic. We created this systematic review aiming to gather reliable scientific evidence to help examine the success of repurposing antipsychotics as possible candidates for numerous viral infections, particularly SARS- CoV2 infection. As of August 2024, we carried out random effect meta-analysis on many clinical studies where most studies provided data supporting the beneficial effect of repurposing APs as antivirals for COVID-19 treatment. On the contrary, one study provided data showing that APs increased the risk of severe COVID-19 and mortality; even though, their use should be examined case by case and psychiatric patients should not be encouraged to discontinue their psychiatric treatment. Based on numerous studies, we observed that AP drugs of the phenothiazine class (promethazine, fluphenazine, chlorpromazine, and thiethylperazine) display a unique pharmacological profile to convergently inhibit SARS-CoV-2. Interestingly, only the phenothiazine class contained at least 10 drugs matching criteria for antiviral effects against SARS- CoV-2. In addition to their efficacy as antipsychotics (and antiemetics in certain cases), this class of agents has also shown antiviral, antibacterial, and anti-prion activities in previous in vitro studies. Therefore, drug repurposing of APs could be a great chance to combat several viral infections while bypassing long-term drug development and providing rapid solutions to emerging health challenges.