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Pathway Description
Baloxavir marboxil Action Pathway
Homo sapiens
Drug Action Pathway
Baloxavir marboxil is a polymerase acidic endonuclease inhibitor used to treat uncomplicated influenza A, B, and Avian. It is specifically a first-in-class cap-dependent endonuclease inhibitor. It is a prodrug of baloxavir with an improved absorption profile than its active metabolite due to the addition of a phenolic hydroxyl group to its structure.
Influenza virus RNA polymerase is made up of three subunits: polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA). The PB2 subunit binds to the cap of host cellular pre-messenger RNA, which allows the polymerase acidic protein to cleave the capped pre-messenger RNA.This is the initial step of mRNA synthesis so viral mRNA transcription can occur.
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. Balaxovir selectively inhibits the polymerase acidic protein, which blocks the initiation of mRNA synthesis which prevents influenza virus proliferation.
References
Baloxavir marboxil Pathway References
Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, Ishida T, Sekino H, Yamada K, Portsmouth S, Kawaguchi K, Shishido T, Arai M, Tsuchiya K, Uehara T, Watanabe A: Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018 Sep 6;379(10):913-923. doi: 10.1056/NEJMoa1716197.
Pubmed: 30184455
Heo YA: Baloxavir: First Global Approval. Drugs. 2018 Apr;78(6):693-697. doi: 10.1007/s40265-018-0899-1.
Pubmed: 29623652
Shirley M: Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza. Drugs. 2020 Jul;80(11):1109-1118. doi: 10.1007/s40265-020-01350-8.
Pubmed: 32601915
Abraham GM, Morton JB, Saravolatz LD: Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza. Clin Infect Dis. 2020 Oct 23;71(7):1790-1794. doi: 10.1093/cid/ciaa107.
Pubmed: 32020174
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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