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Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons.

Gubareva, Larisa V; Mishin, Vasiliy P; Patel, Mira C; Chesnokov, Anton; Nguyen, Ha T; De La Cruz, Juan; Spencer, Sarah; Campbell, Angela P; Sinner, Mallory; Reid, Heather; Garten, Rebecca; Katz, Jackie M; Fry, Alicia M; Barnes, John; Wentworth, David E.

Euro Surveill ; 24(3)2019 Jan.

Article in English | MEDLINE | ID: mdl-30670144

ABSTRACT

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.

Subject(s)

Amino Acid Substitution/drug effects , Antiviral Agents/pharmacology , Drug Resistance, Viral/genetics , Enzyme Inhibitors/pharmacology , Influenza A Virus, H3N2 Subtype/drug effects , Influenza B virus/drug effects , Influenza, Human/drug therapy , Oxazines/pharmacology , Pyridines/pharmacology , Thiepins/pharmacology , Triazines/pharmacology , Amino Acid Substitution/genetics , Antiviral Agents/therapeutic use , Dibenzothiepins , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza B virus/genetics , Influenza B virus/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/virology , Microbial Sensitivity Tests , Morpholines , Pyridones , Seasons , Sentinel Surveillance , United States , Viral Proteins/genetics

ABSTRACT

Subject(s)

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