Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor.

ABSTRACT: Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ReFRAME drug-repurposing library consisting of 12,000 small molecules against RSV. We identify 21 primary candidates including RSV F and N protein inhibitors, five HSP90 and four IMPDH inhibitors. We select lonafarnib, a licensed farnesyltransferase inhibitor, and phase III candidate for hepatitis delta virus (HDV) therapy, for further follow-up. Dose-response analyses and plaque assays confirm the antiviral activity (IC₅₀: 10-118 nM). Passaging of RSV with lonafarnib selects for phenotypic resistance and fixation of mutations i

SUBMITTER: Sake SM 

PROVIDER: S-EPMC10853176 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature