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Drugs of the Future
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Drugs Fut 2018, 43(6): 379
ISSN 0377-8282
e-ISSN 2013-0368
Copyright 2018 Clarivate
CCC: 0377-8282
DOI: 10.1358/dof.2018.043.06.2812618
Baloxavir marboxil. Influenza virus cap-dependent endonuclease (CEN) inhibitor, Anti-influenza agent
Cole, P.
Influenza represents an important risk to public health through both seasonal epidemics and occasional, potentially devastating pandemics. The efficacy of the treatments employed so far, M2 proton channel blockers and neuraminidase inhibitors, is limited and threatened by the emergence of resistance. Numerous approaches are under study for the much needed development of treatments for influenza, and among them is the use of compounds that interfere with the activity of the endonuclease subdomain of the viral RNA polymerase, which cleaves 5' caps from host mRNAs, allowing translation of viral mRNAs by the host ribosome. The "cap-snatching" mechanism within infected cells results in capped RNAs that are used as transcription primers and is essential to virus transcription. Few compounds with this novel mechanism of action have reached advanced levels of development, but one, baloxavir marboxil, demonstrated activity against seasonal influenza strains as well as oseltamivir-resistant strains and avian influenza strains in preclinical studies. Clinical development has progressed into phase III, with the positive results from a large phase III trial leading to approval in Japan, while another global phase III trial is underway.

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