Novel Antiviral Molecules against Ebola Virus Infection.
Int J Mol Sci
; 24(19)2023 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-37834238
ABSTRACT
Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluciferase-based protein complementation assay (NPCA) and isolated two compounds that disrupt the interaction of the EBOV protein fragment VP35IID with the N-terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose that the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, our data support further testing of the compounds in other species, as well as against other negative-sense RNA viruses.
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Base de dados:
MEDLINE
Assunto principal:
Doença pelo Vírus Ebola
/
Ebolavirus
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article