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Table 1 NAI treatment-emergent H1 HA mutations included in current FDA-approved NAI package inserts

From: Influenza A virus hemagglutinin mutations associated with use of neuraminidase inhibitors correlate with decreased inhibition by anti-influenza antibodies

H1 HA mutation included in NAI package insertsa

HA mutations selected in cell culture/associated with reduced susceptibility to NAI in cell culture

Strains containing corresponding treatment-emergent HA mutation

Strains from untreated patients containing corresponding HA mutation (or HA mutation at the same residue)

Corresponding NAI package insert

HA mutation (if different from listed) and/or stain, in which the HA mutation was observed

NA changes observed together with corresponding HA mutation

D125Sb (129)

A/Puerto Rico/8/34 (H1N1) [14]

̶

̶

N125D, A(H1N1)pdm09 [18, 19]

RAPIVAB® [14]

L151P (154)

H151Q, A/Wuhan/259/95 (H1N1) [20]

E119V

A(H1N1)pdm09 [21]

̶

RELENZA® [13]

V152I (155)

T152A, NWS/G70C (H1N9) [6]c,d

̶

̶

A(H1N1)pdm09 [18, 21, 22]

RELENZA® [13]

G155E (158)

A(H1N1)pdm09 [10]c,d

N146S

̶

̶

RELENZA® [13]

S162 Ne (165)

NWS/G70C (H1N9) [7]c,d

̶

A(H1N1)pdm09 [23]

A(H1N1)pdm09 [21, 22, 24]

RELENZA® [13]

S183P (186)

S183F, NWS/G70C (H1N9) [7]c,d

E119G

̶

A(H1N1)pdm09 [18, 23]

RELENZA® [13]

A197T (200)

A/WSN/33 (H1N1) [9]d

Deletion 92–362

̶

A(H1N1)pdm09 [23]

RELENZA® [13]

R208K (211)

A/Puerto Rico/8/34 (H1N1) [14]

̶

̶

̶

RAPIVAB® [14]

D222G (225)

A/Hokkaido/15/02 (H1N1) [11]c

Y155H, V114I

̶

A(H1N1)pdm09 [18, 21,22,23]

RELENZA® [13]

  1. “ ̶” - not identified
  2. aHA1 mutations were identified in a variety of strains and reported using different numbering systems. Numbering in this table is subtype-specific and based on corresponding positions in A/California/04/2009 (H1N1) as described previously [25]. Numbering begins after the predicted signal peptide. H3 HA numbering is shown in parenthesis
  3. bSubstitution could not be reliably mapped to the HA structure due to ambiguous HA numbering coordinates (the system of numbering could not be unambiguously determined based on the available information or did not match the expected wild-type amino acid in the reported strain)
  4. cHA mutation independently reduced susceptibility to NAIs in cell culture
  5. dDrug-dependent phenotype was demonstrated in cell culture
  6. eHA1 mutation introduces potential N-linked glycosylation site