key: cord-0756611-qqekmxc7 authors: Girgis, Ragy R.; Lieberman, Jeffrey A. title: Anti-viral properties of antipsychotic medications in the time of COVID-19 date: 2020-11-30 journal: Psychiatry Res DOI: 10.1016/j.psychres.2020.113626 sha: 6fd69885c6c34f4d6e8cef7a6db64dad049367af doc_id: 756611 cord_uid: qqekmxc7 nan Available online 30 November 2020 0165-1781/© 2020 Elsevier B.V. All rights reserved. Dear Editor, The study by Gordon et al. in Nature (Gordon et al., 2020) identified human proteins with which SARS-CoV-2 interacts, then examined the affinities of FDA-approved compounds for these proteins and their potential antiviral effects. Among the drugs that had significant affinity was haloperidol, a first-generation antipsychotic drug which interacts with sigma receptors and was proposed as an agent with potential antiviral properties. This finding follows prior studies that found antiviral and antimicrobial effects of specific antipsychotic medications. For example, chlorpromazine, a phenothiazine drug, may inhibit endocytosis (Dutta and Donaldson, 2012) of coronaviruses. In fact, several studies have demonstrated that chlorpromazine substantially inhibits MERS-CoV and/or SARS-CoV-2 related viruses in vitro (Cong et al., 2018; Dyall et al., 2014; Inoue et al., 2007) . One group made the observation that patients in their psychiatric hospital seem to have a lower rate of symptomatic COVID-19 infection than staff (Plaze et al., 2020) and propose to conduct a clinical trial of chlorpromazine for symptomatic COVID-19 infection. These antiviral effects are mediated by off-target (non-D2 receptor effects) extra-CNS effects on Sigma and Histamine receptors, among other potential targets. One question is whether the potential antiviral effects of antipsychotic medications are achievable at concentrations which produce their behavioral effects. For example, many antipsychotic drugs are active at nanomolar concentrations, whereas their antiviral effects appear to require at least micromolar concentrations. Despite this limitation, a potential clinical application of such drugs with putative antiviral activity (like haloperidol and chlorpromazine) could be their prioritization among the various drugs in their class for behavioral control of patients in treatment settings such as nursing homes with vulnerable populations to SARS-CoV-2 infection. R. Girgis acknowledges research support from Otsuka, Allergan/ Forest, BioAvantex and Genentech as well as royalties and/or advances from books on mental health published by Wipf and Stock and Routledge/Taylor and Francis. J. Lieberman has received support administered through his institution in the form of funding or medication supplies for investigator-initiated research from Lilly, Denovo, Biomarin, Novartis, Taisho, Teva, Alkermes, and Boehringer Ingelheim, and is a member of the advisory board of Intracellular Therapies and Pierre Fabre. He neither accepts nor receives any personal financial remuneration for consulting, advisory board or research activities. He holds a patent from Repligen and receives royalty payments from SHRINKS: The Untold Story of Psychiatry. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells Search for inhibitors of endocytosis: intended specificity and unintended consequences Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted Repurposing chlorpromazine to treat COVID-19: the recovery study