Table 1.
BXA susceptibility of recombinant influenza A and B viruses carrying I38T/F/M PA substitution
| Influenza virus | Abbreviation | PA 38 genotype* | Virus titer (Log10TCID50/mL) with BXA treatment (nM)† | Plaque reduction EC50 ± SEM (nM)‡ | Fold increase EC50 over I38-WT | |||
| 0 | 1 | 10 | 100 | |||||
| rg-A/California/04/2009 (H1N1)pdm09 | A/CA/04 | IWT | 5.7 | 1.1 | < | < | 0.3 ± 0.1 | − |
| T | 5.3 | 5.2 | 4.0 | 0.8 | 21.0 ± 7.6 | 70.0 | ||
| F | 5.0 | 4.2 | 2.0 | < | 2.2 ± 0.5 | 7.3 | ||
| M | 4.8 | 3.8 | 3.3 | < | 2.5 ± 1.4 | 8.3 | ||
| rg-A/Texas/71/2017 (H3N2) | A/TX/71 | IWT | 7.0 | 3.2 | < | < | 0.2 ± 0.1 | − |
| T | 6.3 | 6.3 | 5.9 | 4.0 | 18.4 ± 2.1 | 92.0 | ||
| F | 6.9 | 5.6 | 4.9 | < | 3.2 ± 0.6 | 16.0 | ||
| M | 7.6 | 7.0 | 5.1 | 2.3 | 4.1 ± 1.6 | 21.0 | ||
| rg-B/Brisbane/60/2008 (Victoria) | B/BR/60 | IWT | 6.6 | 6.1 | 4.6 | < | 2.9 ± 1.1 | − |
| T | 6.2 | 4.7 | 5.2 | 4.3 | 37.0 ± 9.0 | 15.0 | ||
| F | 3.7 | 3.7 | 3.8 | < | ND | ND | ||
| M | 7.0 | 6.8 | 6.3 | 4.3 | 22.0 ± 5.6 | 8.3 | ||
| rg-B/Phuket/3073/2013 (Yamagata) | B/PH/3073 | IWT | 7.1 | 6.8 | 5.9 | < | 3.4 ± 0.8 | − |
| T | 6.4 | 6.5 | 6.1 | 5.4 | 42.0 ± 3.0 | 12.4 | ||
| F | 5.7 | 5.8 | 5.5 | 3.5 | 27.0 ± 10.5 | 8.0 | ||
| M | 6.8 | 6.8 | 6.3 | 4.6 | 19.0 ± 4.4 | 6.0 | ||
<, mean value was below the assay limit of detection (0.75-Log10TCID50/mL); ND, not determined; −, not applicable.
Amino acid identity at residue 38 of the PA protein, introduced by reverse genetics system.
Virus yield (Log10 TCID50/mL) is from virus-infected MDCK cells (MOI 0.01; n = 3 wells per virus) at 72 or 96 hpi with BXA (0 nM to 100 nM) treatment. Mean values are from one of three experiments. Limit of detection = 0.75-Log10 TCID50/100 mL.
Reduction of plaque formation number from virus-infected MDCK cells (50 PFU to 80 PFU per well; n = 3 wells per drug concentration per virus) at 72 hpi or 120 hpi. Mean values from three independent experiments are presented ± SEM.