Rev Med Virol . Fitness of influenza A and B viruses with reduced susceptibility to baloxavir: A mini-review

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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 ¹ , Amel Saim-Mamoun ¹ , Guy Boivin ¹



Affiliations

• PMID: 32975358
• DOI: 10.1002/rmv.2175

Abstract

Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu^? ), zanamivir (Relenza^? ), peramivir (Rapivab^? ) and laninamivir (Inavir^? ), 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.