Antiviral activity of sertindole, raloxifene and ibutamoren against transcription and replication-competent Ebola virus-like particles

Abstract

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 M, a 50% cytotoxic concentration of 42.4 M, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds. [BMB Reports 2020; 53(3): 166-171] BMB Rep. 2020; 53(3): 166-171 www.bmbreports.org

Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

“…Raloxifene has been found to have an in vitro antiviral activity, in terms of inhibition of viral replication and/or infection, against EBOV [ 54 , 76 , 77 ], HCV [ 78 , 79 ], HBV [ 80 ], and Zika virus [ 81 ]. Further, it showed efficacy in human female cells from nasal epithelium, against the influenza virus A [ 82 ].…”

Estrogen Receptor Modulators in Viral Infections Such as SARS−CoV−2: Therapeutic Consequences

“…These mechanisms were also dependent on the interaction of hormones with their receptors. The inhibitory effect of estrogens on replication was documented [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. in a panel of viruses (for particulars see Table 1 ).…”

Repurposing Psychotropic Agents for Viral Disorders: Beyond Covid

“…As shown in Tables 1 and 2, these include Fluphenazine (EBOV, HCV, MERS-CoV, SARS-CoV), 8,11 Perphenazine GOLDEN ET AL. (CHIKV, EBOV, MERS-CoV, SFV), 8,17,27 Prochlorperazine (DENV, EBOV, EBV, HCV, JEV), 8,11,20,28,29 Thioproperazine (EBOV), 30 Thioridazine (CHIKV, EBOV,HCV, SFV), 8,11,17,31 Trifluoperazine (EBOV, EBV, HCV, HIV, influenza, JV, measles, SARS-CoV), 11,15,20,[29][30][31][32][33][34][35] Triflupromazine (EBOV, HCV, MERS, and variable activity against SARS). 8,11,27,35,36 Promazine has shown in vitro activity against HCV 11 and SARS-CoV, but was inactive against SARS-CoV in a mouse model.…”

“…(CHIKV, EBOV, MERS-CoV, SFV), 8,17,27 Prochlorperazine (DENV, EBOV, EBV, HCV, JEV), 8,11,20,28,29 Thioproperazine (EBOV), 30 Thioridazine (CHIKV, EBOV,HCV, SFV), 8,11,17,31 Trifluoperazine (EBOV, EBV, HCV, HIV, influenza, JV, measles, SARS-CoV), 11,15,20,[29][30][31][32][33][34][35] Triflupromazine (EBOV, HCV, MERS, and variable activity against SARS). 8,11,27,35,36 Promazine has shown in vitro activity against HCV 11 and SARS-CoV, but was inactive against SARS-CoV in a mouse model. 35 Other Categories of Psychotropics Also Have Drug Repurposing Potential As extensively reviewed 37 lithium (chloride or carbonate), a mood stabilizer, has been evaluated against DENV, HCV, HIV, HSV-1 and 2, influenza, and measles and showed activity against all.…”

“…Maprotiline/277/0.6 mg/mL = 0.18 mM EBOV 27,52 In vitro Entry Histamine H2 receptor inhibitor Mianserin/264/0.15 mg/mL = 0.06 mM EBOV 46 In vitro Entry MARV 46 In vitro In vitro…”