Unknown

Dataset Information

0

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].

SUBMITTER: Yoon YS 

PROVIDER: S-EPMC7118351 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Yoon Yi-Seul YS   Jang Yejin Y   Hoenen Thomas T   Shin Heegwon H   Lee Younghoon Y   Kim Meehyein M  

BMB reports 20200301 3


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  ...[more]

Similar Datasets

| S-EPMC4335594 | biostudies-other
| S-EPMC7166701 | biostudies-literature
| S-EPMC5876392 | biostudies-literature
| S-EPMC3642163 | biostudies-literature
| S-EPMC104478 | biostudies-literature
| S-EPMC5870946 | biostudies-literature
| S-EPMC8303422 | biostudies-literature
| S-EPMC3754039 | biostudies-literature
| S-EPMC7359519 | biostudies-literature
| S-EPMC4342244 | biostudies-literature