tetano
Editor, Senior Moderator
Rev Med Virol
. 2020 Sep 25;e2175.
doi: 10.1002/rmv.2175. Online ahead of print.
Fitness of influenza A and B viruses with reduced susceptibility to baloxavir: A mini-review
Yacine Abed[SUP] 1 [/SUP], Amel Saim-Mamoun[SUP] 1 [/SUP], Guy Boivin[SUP] 1 [/SUP]
Affiliations
Abstract
Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu[SUP]?[/SUP] ), zanamivir (Relenza[SUP]?[/SUP] ), peramivir (Rapivab[SUP]?[/SUP] ) and laninamivir (Inavir[SUP]?[/SUP] ), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti-influenza agents. Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease activity of the influenza PA protein, was approved in the United States and Japan in 2018. Baloxavir acid (BXA), the active compound of BXM, demonstrated a potent in vitro activity against different types/subtypes of influenza viruses including seasonal influenza A/B strains as well as avian influenza A viruses with a pandemic potential. A single oral dose of BXM provided virological and clinical benefits that were respectively superior or equal to those displayed by the standard (5 days, twice daily) oseltamivir regimen. Nevertheless, BXM-resistant variants have emerged at relatively high rates in BXM-treated children and adults. Consequently, there is a need to study the fitness (virulence and transmissibility) characteristics of mutants with a high potential to emerge as such variants can compromise the clinical usefulness of BXM. The purpose of this manuscript is to review the fitness properties of influenza A and B isolates harbouring mutations of reduced susceptibility to BXA.
Keywords: baloxavir acid; baloxavir marboxil; fitness; influenza A; influenza B; resistance.
. 2020 Sep 25;e2175.
doi: 10.1002/rmv.2175. Online ahead of print.
Fitness of influenza A and B viruses with reduced susceptibility to baloxavir: A mini-review
Yacine Abed[SUP] 1 [/SUP], Amel Saim-Mamoun[SUP] 1 [/SUP], Guy Boivin[SUP] 1 [/SUP]
Affiliations
- PMID: 32975358
- DOI: 10.1002/rmv.2175
Abstract
Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu[SUP]?[/SUP] ), zanamivir (Relenza[SUP]?[/SUP] ), peramivir (Rapivab[SUP]?[/SUP] ) and laninamivir (Inavir[SUP]?[/SUP] ), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti-influenza agents. Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease activity of the influenza PA protein, was approved in the United States and Japan in 2018. Baloxavir acid (BXA), the active compound of BXM, demonstrated a potent in vitro activity against different types/subtypes of influenza viruses including seasonal influenza A/B strains as well as avian influenza A viruses with a pandemic potential. A single oral dose of BXM provided virological and clinical benefits that were respectively superior or equal to those displayed by the standard (5 days, twice daily) oseltamivir regimen. Nevertheless, BXM-resistant variants have emerged at relatively high rates in BXM-treated children and adults. Consequently, there is a need to study the fitness (virulence and transmissibility) characteristics of mutants with a high potential to emerge as such variants can compromise the clinical usefulness of BXM. The purpose of this manuscript is to review the fitness properties of influenza A and B isolates harbouring mutations of reduced susceptibility to BXA.
Keywords: baloxavir acid; baloxavir marboxil; fitness; influenza A; influenza B; resistance.