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].
Baloxavir 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDCK-SIAT1 cells
0.006 to 1.56 nM
24 h
To evaluate the synergistic antiviral activity of Baloxavir and Oseltamivir. Results showed that Baloxavir and Oseltamivir had synergistic effects at low concentrations, even against viruses with reduced susceptibility to Baloxavir.
mBio. 2022 Aug 30;13(4):e0105622.
Baloxavir 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Cynomolgus macaques
H7N9 highly pathogenic avian influenza virus infection model
Intragastric administration
1 mg/kg body weight
Single dose on day 1 post-infection
To evaluate the efficacy of Baloxavir against H7N9 highly pathogenic avian influenza virus in cynomolgus macaques. Results showed that virus titers in the Baloxavir group were significantly lower than in other treatment groups, and levels of IFN-α and IFN-β in plasma were higher.
Antimicrob Agents Chemother. 2021 Feb 17;65(3):e01825-20
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