Fig. 1. 4′-FlU is a potent broad-spectrum antiviral.
(A) Chemical structure of 4′-FlU. (B) Virus yield reduction of RSV clinical isolates 6A8, 16F10, 2-20, and recombinant recRSV-A2line19F-[mKate] [(A) or (B) antigenic subgroup]. (C) HEp-2, MDCK, BHK-T7, and BEAS-2B cell lines were assayed for reduction in cell metabolism by 4′-FlU. (D and E) recRSV-A2line19F-[FireSMASh] dose response inhibition and cytotoxicity assay with human airway epithelial (HAE) cells (D) from two donors in the presence of indicated 4′-FlU concentrations (E). (F) Dose-response inhibition of a panel of recombinant mononegaviruses by 4′-FlU. (G) Dose-response inhibition of recSARS-CoV-2-[Nluc] and virus yield reduction of alpha, gamma, and delta VoC isolates by 4′-FlU. (H) Dose-response inhibition of transiently expressed polymerase complexes from mononegaviruses MeV, RSV, NiV, or HPIV-3 by 4′-FlU (I) recRSV-A2line19F-[FireSMASh]-infected cells were treated with 10 μM of 4′-FlU and serial dilutions of exogenous nucleotides in extracellular media. Viral activity was determined by reporter activity. Symbols represent independent repeats (B), (E), (G), (H), and (I) or mean with standard deviation (C) and (F), and lines represent means. n ≥ 3, EC50s and CC50s are reported in tables S1 and S2, and all source data are provided in data S2.