Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.

ABSTRACT: Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC₅₀ changes in A and B viruses, respectively. The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonucleas

SUBMITTER: Omoto S 

PROVIDER: S-EPMC6018108 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature