. Author manuscript; available in PMC: 2021 Nov 10.

Published in final edited form as: J Infect Dis. 2017 Sep 15;216(Suppl 4):S566–S574. doi: 10.1093/infdis/jiw625

Table 3.

Inhibition Profiles of Recombinant Neuraminidase (NA) Proteins of Influenza A/Shanghai/2/2013(H7N9) Virus, Based on the Fluorescence-Based NA Inhibition Assay

NA Change (N2) or Group^a	NA change (Avian N9)	IC₅₀,^b nM, Mean ± SD (Fold Change^c)
NA Change (N2) or Group^a	NA change (Avian N9)	Oseltamivir	Zanamivir	Peramivir	Laninamivir
Normal inhibition
None	None	0.27 ± 0.01 [1]	0.50 ± 0.05 [1]	0.07 ± 0.01 [1]	0.53 ± 0.03 [1]
Reduced or highly reduced inhibition
Reduced inhibition by at least 1 NA inhibitor
R152K	R153K	0.09 ± 0.01 [1]	2.71 ± 0.06 [5]	0.19 ± 0.01 [3]	8.40 ± 0.69 [16^d]
I222K	I224K	12.48 ± 1.12 [46^d]	8.32 ± 0.22 [17^d]	0.80 ± 0.02 [11^d]	14.32 ± 1.06 [27^d]
T247P	T249P	7.34 ± 0.78 [27^d]	34.60 ± 2.36 [69^d]	0.30 ± 0.05 [4]	4.51 ± 0.33 [9]
N294S	N296S	0.54 ± 0.05 [2]	4.83 ± 0.45 [10^d]	0.10 ± 0.01 [1]	1.35 ± 0.06 [3]
R371K	R372K	18.91 ± 13.0 [70^d]	32.24 ± 2.55 [64^d]	2.00 ± 0.21 [29^d]	9.94 ± 0.95 [19^d]
Highly reduced inhibition by oseltamivir
E119V	E120V	45.64 ± 0.98 [169^d]	4.42 ± 0.30 [9]	0.11 ± 0.01 [1]	0.86 ± 0.05 [2]
I222R	I224R	38.55 ± 3.61 [143^d]	18.89 ± 2.02 [38^d]	3.10 ± 0.13 [44^d]	33.54 ± 1.70 [63^d]
H274Y	H276Y	28.32 ± 2.30 [105^d]	1.09 ± 0.08 [2]	0.66 ± 0.05 [9]	1.09 ± 0.08 [2]
Highly reduced inhibition by oseltamivir and peramivir
R292K	R294K	>10 000 [>10 000^d]	33.25 ± 2.65 [67^d]	174.10 ± 8.38 [2487^d]	16.40 ± 1.82 [31^d]
Highly reduced inhibition by zanamivir
E119A	E120A	5.01 ± 0.59 [19^d]	114.12 ± 9.50 [228^d]	1.43 ± 0.17 [20^d]	32.8 ± 2.01 [62^d]
E276D	E278D	3.64 ± 1.30 [13^d]	213.52 ± 78.88 [427^d]	1.74 ± 0.72 [25^d]	47.51 ± 13.50 [90^d]
Highly reduced inhibition by zanamivir and peramivir
E119G	E120G	0.42 ± 0.07 [2]	209.54 ± 10.07 [419^d]	3.35 ± 0.25 [48^d]	65.93 ± 2.68 [124^d]
Highly reduced inhibition by zanamivir, peramivir, and laninamivir
E119D	E120D	3.77 ± 0.18 [14^d]	718.14 ± 70.11 [1436^d]	28.75 ± 3.43 [411^d]	203.06 ± 38.68 [383^d]
Q136K	Q137K	0.08 ± 0.01 [1]	350.91 ± 32.19 [702^d]	9.19 ± 0.83 [131^d]	166.12 ± 11.94 [313^d]
Control A(H1N1)pdm09 viruses^e
None	None	0.18 ± 0.06	0.15 ± 0.03	0.04 ± 0.01	0.12 ± 0.01
H274Y	H276Y	149.72 ± 30.40 [812^d]	0.18 ± 0.02 [1]	14.92 ± 1.89 [348^d]	0.26 ± 0.02 [2]

Abbreviations: A(H1N1)pdm09, 2009 pandemic influenza A(H1N1) virus; IC₅₀, half-maximal inhibitory concentration; recN9, recombinant N9.

Amino acid numbering is based on the N2 and N9 numbering schemes. See also Table 2.

The IC₅₀ denotes the concentration of a NA inhibitor that reduces the NA activity of recNA9 by 50% relative to NA activity without the inhibitor. Values represents the average of at least 3 independent experiments.

Fold change relative to the mean IC₅₀ of the recN9 wild-type NA protein. Fold-change values of each recN9 were interpreted using criteria established by the World Health Organization Influenza Antiviral Working Group [18].

Fold change >10 (ie, reduced/highly reduced inhibition).

A/California/12/2012(H1N1)pdm09 wild-type (none) and A/Texas/23/2012(H1N1)pdm09 (H274Y).