Extended Data Table 2 Deep-sequence analysis of PA protein amino acid substitutions in virus-positive brain or lung tissue

From: Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk

Mouse ID	Tissue	Inoculation route	Treatment regimen	PA a.a change^{a, b} (% Frequency, read count/coverage)
33	Brain	Oral	BXA 25 mg/kg	PA V100I (7.0%, 545/7774)
				PA P105L (8.02%, 625/7791)
34	Brain	Oral	BXA 25 mg/kg	PA T97I (95.0%, 9724.0/10238)
43	Brain	Oral	BXA 5 mg/kg	No Changes
44	Brain	Oral	BXA 5 mg/kg	No Changes
45	Brain	Oral	BXA 5 mg/kg	PA N27G (14.6%, 511/3505)
65	Brain	Intranasal	BXA 5 mg/kg	No Changes
66	Brain	Intranasal	BXA 5 mg/kg	No Changes
67	Brain	Intranasal	BXA 5 mg/kg	No Changes
145	Brain	Ocular	Non-treated	PA M21V (99.3%, 3278/3300)
146	Brain	Ocular	Non-treated	No Changes
147	Brain	Ocular	Non-treated	No Changes
156	Brain	Oral	Non-treated	No Changes
157	Brain	Oral	Non-treated	No Changes
158	Brain	Oral	Non-treated	No Changes^c
167	Brain	Intranasal	Non-treated	PA T97I (31.4%, 2832/9014)
168	Brain	Intranasal	Non-treated	No Changes^c
60	Brain	Intranasal	Non-treated	PA T97I (8.2%, 856/10385)
33	Lung	Oral	BXA 25 mg/kg	No Changes
34	Lung	Oral	BXA 25 mg/kg	PA I38T (7.0%, 342/4887)
43	Lung	Oral	BXA 5 mg/kg	PA M21I (21.5%, 741/3440)
44	Lung	Oral	BXA 5 mg/kg	No Changes
45	Lung	Oral	BXA 5 mg/kg	No Changes
56	Lung	Intranasal	BXA 25 mg/kg	PA N27G (34.1%, 1144/3353)
				PA I38T (16.5%, 658/4001)
65	Lung	Intranasal	BXA 5 mg/kg	PA I38T (74.4%, 2980/4173)
66	Lung	Intranasal	BXA 5 mg/kg	No Changes
67	Lung	Intranasal	BXA 5 mg/kg	PA M21I (38.35%, 1202/3140)
145	Lung	Ocular	Non-treated	PA M21I (98.8%, 2732/2762)
146	Lung	Ocular	Non-treated	R82I (66.0%, 6208/9405)
147	Lung	Ocular	Non-treated	No Changes
156	Lung	Oral	Non-treated	No Changes
157	Lung	Oral	Non-treated	No Changes
158	Lung	Oral	Non-treated	No Changes
167	Lung	Intranasal	Non-treated	T97I (31.1%, 2658/8555)
168	Lung	Intranasal	Non-treated	No Changes^c
60	Lung	Intranasal	Non-treated	T97I (7.7%, 796/10386)

^a Identified from Illumina sequencing of PA fragments comprising nucleotides 8-607
^b Amino acid variant calling in CLC Genomics was performed with a variant frequency cutoff of 5% for ≥1000 reads at the target region
^c Sample contained 1 synonymous change in the coding region
a.a. = amino acid; bolded text represents a.a. substitution strongly correlated with clinical BXA reduced susceptibility.

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Extended Data Table 2 Deep-sequence analysis of PA protein amino acid substitutions in virus-positive brain or lung tissue

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