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Pharmaceuticals -> Anti infectives for systemic use -> Antivirals for systemic use

Pharmaceuticals -> Listed in ZINC15

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P273, P391, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Baloxavir marboxil

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Baloxavir marboxil is an antiviral drug that works against influenza virus to block viral replication. It has an 50% inhibitory concentration (IC₅₀) of 1.4 to 3.1 nM for influenza A viruses and 4.5 to 8.9 nM for influenza B viruses in a polymerase acidic (PA) endonuclease assay. In murine models of influenza and avian influenza A, baloxavir reduced pulmonary viral loads and increased survival rates of mice. The reduction of viral titer was observed within 24 hours of administration, in a dose-dependent manner.

The influenza virus RNA polymerase complex is a heterotrimer made up of three protein subunits - polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA). This polymerase complex is an influenza virus-specific enzyme essential for viral gene transcription and replication, with its subunits playing different roles in viral mRNA synthesis. The PB2 subunit binds to the cap of host cellular pre-messenger RNA, allowing the PA protein - a cap-dependent endonuclease - to cleave the capped pre-messenger RNA. This initial step of mRNA synthesis by the PA protein, also known as the "cap-snatching process," provides an RNA primer for the PB1 subunit, which carries out its RNA-dependent RNA polymerase function to proceed with viral mRNA transcription. After administration, the prodrug baloxavir marboxil is almost completely hydrolyzed by esterases in the gastrointestinal lumen, intestinal epithelium, liver and blood to its active metabolite, baloxavir. Baloxavir selectively inhibits the PA protein, blocking the initiation of mRNA synthesis and ultimately influenza virus proliferation. Cap-dependent endonuclease is a highly conserved region across influenza strains; however, baloxavir is still vulnerable to resistance because amino acid substitutions in the PA protein can lead to reduced viral susceptibility to baloxavir.