Baloxavir, derived from the prodrug Baloxavir marboxil, is a potent, selective cap-dependent endonuclease (CEN) inhibitor of the PA subunit of influenza A and B viral polymerase, a first-in-class inhibitor of viral RNA transcription and replication, and possesses potent antiviral activity. Baloxavir inhibits both cap-dependent endonuclease (CEN) and cap-dependent endonuclease (CEN). Baloxavir inhibits cap-dependent endonuclease (CEN) and CEN/RdRp activity with IC50 values of 2.5 nM and 1.6 nM, respectively, while the inhibitory efficacy against RdRp activity is low (IC50 >40 nM)[1][2].The median EC50 values of Baloxavir against A/H1N1pdm, A/H3N2 and B viruses were 17.96 nM, 4.48 nM and 18.67 nM, respectively[1].Baloxavir inhibits viral RNA transcription by inhibiting cap-dependent endonuclease (CEN) activity, and inhibits viral replication in infected cells without cytotoxicity in cytopathic effect assays. Baloxavir has a broad spectrum of efficacy against various subtypes of influenza A viruses (H1N2, H5N1, H5N2, H5N6, H7N9 and H9N2). In addition, sequential passaging of the viruses in the presence of Baloxavir resulted in the isolation of PA/I38T variants with reduced susceptibility to BXA. Baloxavir showed high potency to inhibit CEN activity in the tested influenza A and B virus ribonucleoprotein complexes (vRNPs), with mean IC50 values of 1.4-3.1 nM and 4.5-8.9 nM, respectively, indicating broad-spectrum activity. Baloxavir was highly potent against influenza A and B viruses, with mean EC90 values of 0.46-0.98 nM and 2.2-3.4 nM, respectively[2].
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