Table 4 Functional properties of non-synonymous amino acid substitutions reported in the cohort. Where functional properties have not been investigated in the literature ‘Unknown’ is reported
Mutation | Functional properties |
|---|---|
NSP1 | |
 R124C | Destabilisation of NSP1, increasing protein flexibility; may impact immune response or viral replication [67]. Substitutions at R124/K125 have previously been shown to increase destabilisation promoting host RNA decay/reducing host mRNA translation by destabilising binding to 40S ribosomal subunit [68] |
NSP2 | |
 A26V | Found in a delta subvariant AY.29 [69] |
 S32L | Unknown |
NSP3 | |
 A480V | Unknown |
 S1424F | Unknown |
 A1736V | Prevalent in many delta subvariants [70] |
NSP4 | |
 V180I | Unknown |
 T189I | Unknown |
 M324I | Found in delta subvariants. Affects the hydrophobic interactions to L321, L323 of the opposite helix; however, effects on stability remain unknown [71] |
NSP5 | |
 M82I | Detected as a treatment-emergent mutation (n = 3) to Paxlovid in the EPIC-HR trial [72] |
NSP8 | |
 R51C | Unknown |
NSP12 | |
 D62Y | Unknown |
 P323L | Located in the interface domain and gives an increased replicative advantage [11] |
 V410A | Located near the NSP12-NSP7 interface, this mutation has been suggested to lead to alterations in the RNA dependent RNA polymerase activity due to its location in the complex [73] |
NSP15 | |
 V127F | Found in Omicron lineages |
NSP16 | |
 M65I | Unknown |
S | |
 E96D | Found in Omicron sublineages and emerged in an immuno-compromised patient on day 72 [74] |
 V143F | In the β9-β10 loop of the NTD, V143 forms rigid interactions so F143 could alter hydrophobicity [75] and be important in antibody recognition. Present in Alpha sublineages |
 T478K | In the RBD, enhances stabilisation of RBD-ACE2 complex [76] and is found in Delta and Omicron sublineages |
 D614G | The first Spike mutation reported, found in all lineages and facilitates an open state of Spike, increasing flexibility and cell entry efficiency [77] |
ORF3a | |
 Q57H | Confers an increased dimeric conformation and stability, contributing to the reduced permeability of ions which causes decreased antigenic properties and aids viral evasion of the immune system which could enhance viral pathogenesis overall [78] |
N | |
 S194L | This mutation has been associated with more severe disease [79] and offers a replicative advantage to the virus [80] |
 T362I | Unknown |