Abstract
In our ongoing efforts to identify baloxavir resistance markers, we demonstrated that the influenza A polymerase acidic (PA) protein E23R substitution is genetically stable, increases baloxavir EC50 values (13- to 19-fold vs. wild-type), synergizes with PA I38T, and only modestly decreases viral fitness. E23R is, therefore, a potential threat to baloxavir treatment efficacy.
Keywords:
Antiviral; Baloxavir; E23R; Endonuclease; Influenza; Polymerase acidic.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use
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Dibenzothiepins
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Drug Resistance, Viral / genetics
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Humans
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Influenza A virus* / genetics
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Influenza, Human* / drug therapy
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Morpholines
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Oxazines / pharmacology
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Oxazines / therapeutic use
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Pyridines / pharmacology
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Pyridones / pharmacology
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Pyridones / therapeutic use
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Thiepins* / pharmacology
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Thiepins* / therapeutic use
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Triazines / pharmacology
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Triazines / therapeutic use
Substances
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Antiviral Agents
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Dibenzothiepins
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Morpholines
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Oxazines
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Pyridines
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Pyridones
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Thiepins
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Triazines
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baloxavir