Novel antiviral molecules against Ebola virus infection

Collados Rodriguez, M. et al. (2023) Novel antiviral molecules against Ebola virus infection. International Journal of Molecular Sciences, 24, 14791. (doi: 10.3390/ijms241914791) (PMID:37834238) (PMCID:PMC10573436)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Collados Rodriguez, Dr Milagros

Creator Roles

Collados Rodriguez, M.: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review and editing, Visualization, Supervision

• Authors: Collados Rodriguez, M., Maillard, P., Journeaux, A., Komarova, A. V., Najburg, V., Sanchez David, R.-Y., Helynck, O., Guo, M., Zhong, J., Baize, S., Tangy, F., Jacob, Y., Munier-Lehmann, H., and Meurs, E. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: International Journal of Molecular Sciences
• Publisher: MDPI
• ISSN: 1661-6596
• ISSN (Online): 1422-0067
• Copyright Holders: Copyright: © 2023 by the authors
• First Published: First published in: International Journal of Molecular Sciences 24: 14791
• Publisher Policy: Reproduced under a Creative Commons licence