[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir
Anton Chesnokov, Mira C Patel, Vasiliy P Mishin, Juan A De La Cruz, Lori Lollis, Ha T Nguyen, Vivien Dugan, David E Wentworth, Larisa V Gubareva
The Journal of Infectious Diseases, jiz472, https://doi.org/10.1093/infdis/jiz472
Published: 21 September 2019
Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold), but also on in vitro replicative fitness. While I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir resistant viruses needed for informed risk assessment.
Cap-dependent endonuclease inhibitor, replicative fitness, polymerase acidic protein, influenza, drug resistance, ferret, baloxavir acid, antiviral
Issue Section: Brief Report
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These authors contributed equally to this article and share first authorship
Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Keywords: Influenza A; Antivirals; Drugs Resistance; Baloxavir.