Review
Chemical Structure and Synthesis of Baloxavir Marboxil, A Novel Endonuclease Inhibitor For The Treatment Influenza : An Overview
Abstract
One drug target that was identifed as a promising candidate for infuenza antiviral drugs is the infuenza virus polymerase complex. The three-component polymerase complex, which is highly conserved and is essential for infuenza virus replication, has received considerable attention as a potential target for infuenza antiviral drugs. Baloxavir marboxil (Xofuza®; hereafter referred to as baloxavir), the prodrug of baloxavir acid, is a frst-in-class, small molecule inhibitor of the cap-dependent endonuclease reaction that is conducted by the polymerase acidic (PA) protein subunit of the infuenza virus polymerase complex. In this review, we summarized the chemical structure, synthesis, mechanism of action, pharmacological activity and synthesis of Baloxavir marboxil, a novel FDA-approved endonuclease inhibitor for the treatment of influenza.
References
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- 19. Tomassini, J., et al., Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2, 4-dioxobutanoic acid compounds. Antimicrobial agents and chemotherapy, 1994. 38(12): p. 2827-2837.
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Year 2022,
Volume: 2 Issue: 3, 91 - 99, 06.07.2022
Abstract
References
- 1. Thompson, W.W., et al., Estimates of US influenza‐associated deaths made using four different methods. Influenza and other respiratory viruses, 2009. 3(1): p. 37-49.
- 2. Falgout, B., R. Miller, and C.-J. Lai, Deletion analysis of dengue virus type 4 nonstructural protein NS2B: identification of a domain required for NS2B-NS3 protease activity. Journal of virology, 1993. 67(4): p. 2034-2042.
- 3. Dong, G., et al., Adamantane-resistant influenza a viruses in the world (1902–2013): frequency and distribution of M2 gene mutations. PloS one, 2015. 10(3): p. e0119115.
- 4. Treanor, J.J., et al., Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. Jama, 2000. 283(8): p. 1016-1024.
- 5. Nicholson, K., et al., Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. The Lancet, 2000. 355(9218): p. 1845-1850.
- 6. Lee, N., et al., Viral loads and duration of viral shedding in adult patients hospitalized with influenza. The Journal of infectious diseases, 2009. 200(4): p. 492-500.
- 7. Belongia, E.A., et al., Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008-2009 (H1N1), and 2007-2008 (H3N2) infections. Jama, 2010. 304(10): p. 1091-1098.
- 8. Hughes, D.L., Review of the patent literature: synthesis and final forms of antiviral drugs tecovirimat and baloxavir marboxil. Organic Process Research & Development, 2019. 23(7): p. 1298-1307.
- 9. FDA Review. [cited 2022 25 May]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210854Orig1s000SumR.pdf.
- 10. Ng, K.E., Xofluza (Baloxavir Marboxil) for the treatment of acute uncomplicated influenza. Pharmacy and Therapeutics, 2019. 44(1): p. 9.
- 11. Ando, Y., et al., Pharmacokinetic and pharmacodynamic analysis of baloxavir marboxil, a novel cap-dependent endonuclease inhibitor, in a murine model of influenza virus infection. Journal of Antimicrobial Chemotherapy, 2021. 76(1): p. 189-198.
- 12. Dufrasne, F., Baloxavir marboxil: An original new drug against influenza. Pharmaceuticals, 2021. 15(1): p. 28.
- 13. Yang, T., Baloxavir marboxil: the first cap-dependent endonuclease inhibitor for the treatment of influenza. Annals of Pharmacotherapy, 2019. 53(7): p. 754-759.
- 14. Louten, J., Virus replication. Essential human virology, 2016: p. 49.
- 15. Jackson, D., R.A. Elderfield, and W.S. Barclay, Molecular studies of influenza B virus in the reverse genetics era. Journal of General Virology, 2011. 92(1): p. 1-17.
- 16. Yuan, S., L. Wen, and J. Zhou, Inhibitors of influenza A virus polymerase. ACS Infectious Diseases, 2018. 4(3): p. 218-223.
- 17. Ju, H., et al., Inhibitors of influenza virus polymerase acidic (PA) endonuclease: contemporary developments and perspectives. Journal of Medicinal Chemistry, 2017. 60(9): p. 3533-3551.
- 18. Noshi, T., et al., In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral research, 2018. 160: p. 109-117.
- 19. Tomassini, J., et al., Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2, 4-dioxobutanoic acid compounds. Antimicrobial agents and chemotherapy, 1994. 38(12): p. 2827-2837.
- 20. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 210854Orig1s000: Clinical review(s). From FDA website. . [cited 2022 30 May]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210854Orig1s000SumR.pdf.
- 21. Koshimichi, H., et al., Safety, tolerability, and pharmacokinetics of the novel anti-influenza agent baloxavir marboxil in healthy adults: phase I study findings. Clinical Drug Investigation, 2018. 38(12): p. 1189-1196.
- 22. Shirley, M., Baloxavir marboxil: a review in acute uncomplicated influenza. Drugs, 2020. 80(11): p. 1109-1118.
- 23. Koshimichi, H., et al., Population pharmacokinetic and exposure-response analyses of baloxavir marboxil in adults and adolescents including patients with influenza. Journal of Pharmaceutical Sciences, 2019. 108(5): p. 1896-1904.
- 24. Kawai, M., et al., Substituted polycyclic pyridone derivative and prodrug thereof. 2018, Google Patents.
There are 24 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences |
| Journal Section | Reviews |
| Authors | |
| Publication Date | July 6, 2022 |
| Published in Issue | Year 2022 Volume: 2 Issue: 3 |
