Table 10 Amino acid positions discussed in literature from the models of both the subtypes for all proteins

M1

115,121,137

Known signatures of host-adaptation [19, 22, 23]

30,142,207,209

Affecting viral production on mutation [27]

121

Affecting viral replication [45]

101

Determinant of temperature sensitivity [46], located in a transcription inhibition site [47] and is also interacting with NEP [48]

M2

11,14,18,20,28,55,57,78,82,89,93

Known signatures of host-adaptation [19, 22, 23, 49]

31

S31N is a known marker for amantadine resistance [28–31]

18,20

Lie next to 17,19 which forms a di-sulphide bond [50]

NS1

18,21,22,53,60,70,81,112,114,171,215,227

Known signatures of host-adaptation [18, 20–23, 51]

215

Required for Crk/CrL-SH3 binding [52]

123

Necessary for interaction with PKR, resulting in an inhibition of eIF2alpha phosphorylation [53]

95

Along with others, has been shown to be necessary for binding p85beta and activating PI3K signaling [54, 55]

220

Part of nuclear localization signal 2 essential for the importin-alpha binding [56]

NEP(NS2)

57,60,70,107

Known signatures of host-adaptation [18, 19, 22, 23, 57]

NP

16,33,100,214,283,313,351,353,357,422

Known signatures of host-adaptation [19–23, 58]

16

D16G shown to decrease pathogenicity several fold [59]

PA

28,55,57,65,256,268,277,356,382,400,409

Known signatures of host-adaptation [19–23, 58]

85,336

Residues 85I and 336 M are deemed important for enhanced polymerase activity in mammalian cells [60]

57,65,85

Shown to be involved in suppressing the host cell protein synthesis during infection [61]

PB1

52,179,216,298,327,336,361,375,581,741

Known signatures of host-adaptation [17, 19, 22, 23, 58]

581

Shown to be conferring temperature sensitivity to human influenza virus vaccine strains [62]

473

Mutation at position 473 has been shown to decrease polymerase activity [63]

PB2

9,44,64,81,105,271,292,368,453,588,613,682,684

Known signatures of host-adaptation [19, 20, 22, 23, 58]

591

591Q is known to mimic the effect of 627 K [64, 65]

271

271A shown to increase polymerase activity in mammalian cells [66]

271,588

Also been shown to be host range determinants [67]

PB1-F2

16,23,42,66,70,73,76

Known signatures of host-adaptation [18, 23]

66

Linked with affecting pathogenicity [68]

NA

46,47,74,147,157,341,351

Under selection pressure with a shift of hosts from birds to humans [58]

344

Calcium ion binds here that stabilizes the molecule (UniProt: Q9IGQ6).

HA

2,6,9,10,14

Signal peptide domain

88,173,220,22

Position 71, 159, 206 and 208 of the fully-mature HA with H3-numbering [69]) are part of the antigenic sites Cb, Sb and Ca of the HA protein, respectively [70, 71]