Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on the Fitness of Contemporary Influenza A(H1N1)pdm09 and A(H3N2) Strains

Abstract Background Baloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substit...

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Veröffentlicht in:	The Journal of infectious diseases 2020-01, Vol.221 (1), p.63-70
Hauptverfasser:	Checkmahomed, Liva, M’hamdi, Zeineb, Carbonneau, Julie, Venable, Marie-Christine, Baz, Mariana, Abed, Yacine, Boivin, Guy
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Substitution Animals Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Cell culture Dibenzothiepins Dogs Drug Resistance, Viral - genetics Experiments Female Fitness Influenza Influenza A Influenza A Virus, H1N1 Subtype - enzymology Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - pathogenicity Influenza A Virus, H3N2 Subtype - enzymology Influenza A Virus, H3N2 Subtype - genetics Influenza A Virus, H3N2 Subtype - pathogenicity Inhibitory Concentration 50 Lung - virology Madin Darby Canine Kidney Cells Major and Brief Reports Mice Mice, Inbred C57BL Morpholines Mutants Mutation Orthomyxoviridae Infections - drug therapy Orthomyxoviridae Infections - virology Oseltamivir Oxazines - pharmacology Oxazines - therapeutic use Phenotype Polymerase chain reaction Pyridines - pharmacology Pyridines - therapeutic use Pyridones RNA-Dependent RNA Polymerase - genetics RNA-Dependent RNA Polymerase - metabolism Thiepins - pharmacology Thiepins - therapeutic use Triazines - pharmacology Triazines - therapeutic use Viral Load - drug effects Viral Proteins - genetics Viral Proteins - metabolism Virulence Virus Replication - drug effects Viruses
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