Novel Antiviral Molecules against Ebola Virus Infection

Autor: Mila Collados Rodríguez, Patrick Maillard, Alexandra Journeaux, Anastassia V. Komarova, Valérie Najburg, Raul-Yusef Sanchez David, Olivier Helynck, Mingzhe Guo, Jin Zhong, Sylvain Baize, Frédéric Tangy, Yves Jacob, Hélène Munier-Lehmann, Eliane F. Meurs
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14791 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms241914791
Popis: 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.
Databáze: Directory of Open Access Journals
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