key: cord-1037696-uiwp36fc authors: Otręba, Michał; Kośmider, Leon; Rzepecka-Stojko, Anna title: Antiviral activity of chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine towards RNA-viruses. A review date: 2020-09-16 journal: Eur J Pharmacol DOI: 10.1016/j.ejphar.2020.173553 sha: f59bb71ee6239bec9b00d47a8b84528b91f349a2 doc_id: 1037696 cord_uid: uiwp36fc In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not seen such mobilization towards one topic in this century. The whole situation makes clear that progress needs to be made in antiviral drug development. The first step to do it is to characterize the potential antiviral activity of new or already existed drugs on the market. Phenothiazines are antipsychotic agents used previously as antiseptics, anthelminthics, and antimalarials. Up to date, they are tested for a number of other disorders including the broad spectrum of viruses. The goal of this paper was to summarize the current literature on activity toward RNA-viruses of such drugs like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine. We identified 49 papers, where the use of the phenothiazines for 23 viruses from different families were tested. Chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine possess anti-viral activity towards different types of viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Additionally, since the drugs display activity at nontoxic concentrations they have therapeutic potential for some viruses, still, further research on animal and human subjects are needed in this field to verify cell base research. inhibitory activity of viral entry by clathrin-mediated endocytosis (prevent the formation of 144 clathrin-coated pits at the cell membrane), it may be used as a potential broad-spectrum 145 inhibitor not only against West Nile virus (WNV) but also MERS-CoV and SARS-CoV, Table 1 . 152 Unfortunately, the assay performer by Wahlbeck et al. (1997) showed that Table 1 . High-throughput drug screening 742 using the Ebola virus transcription-and replication-competent virus-like particle system Characterization of Zika virus endocytic pathways in human 746 glioblastoma cells Chikungunya-748 attributable deaths: A neglected outcome of a neglected disease Potential inhibitors against 2019-nCoV coronavirus M protease 751 from clinically approved medicines Testing of Middle East 754 respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and 758 schizophrenia: effects of antidepressants and antipsychotic drugs Rift Valley fever virus: A review of diagnosis and 765 vaccination, and implications for emergence in Europe Japanese encephalitis virus infection of Vero cells by a cationic amphiphilic drug Middle east respiratory syndrome-coronavirus 771 (MERS-CoV): An updated overview and pharmacotherapeutics Recent discovery and 774 development of inhibitors targeting coronaviruses Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon 778 cell line and virus-based assays Drug targets for corona virus: A systematic 782 review Novel coronavirus (COVID-19) outbreak: A Review of 788 the current literature Virtual screening for potential inhibitors of 790 NS3 protein of Zika virus Therapeutic and toxic blood concentrations of more than 800 793 drugs and other xenobiotics Repurposing of prochlorperazine for 795 use against Dengue virus infection From SARS to MERS, thrusting coronaviruses into the spotlight