Table 2.

Mutations A67V to K417N in spike protein of the Omicron variant: locations, previous association to other SARS-CoV-2 variants and current knowledge about them (December 2021)

S protein substitutions	Location in spike	Previous variants	What is already known about this substitution
A67V	β3-β4 loop of NTD [153]	Eta [153]	Decreased protein stability by − 0.01 [119] Might promote new hydrophobic interconnections in the β3-β4 loop [153]
del69-70	β3-β4 loop of NTD [153]	Alpha, Beta, Eta, and B.1.375 [153, 154]	- Clinical: in a study (n = 25), this single mutation showed prolonged inflammation, viral excretion, and late exacerbation 18 days after [155]. Increased infectivity compared to wild-type [156] Immune: Associated with immune escape [153, 157, 158] - Diagnostic: linked to diagnostic failure in at least one RT-PCR assay [159]; Can be used in diagnostic methods, allied with other mutations, to help to screen high profile variants [154, 160] - Structural: might be related to allosteric changes in S1 conformation [161, 162]
T95I	S1 NTD	Mu; Iota [163]; B.1.617.1; Delta or Delta plus [89, 164]	- Structural: induces changes in the protein [165] e decrease protein stability − 0.78 [119] - Immune: showed a minor increase in resistance to convalescent sera [91] and some evidence linked it to vaccine breakthrough infection [166, 167] - Clinical: does not seem to be relevant to infectivity [19]a, but can be associated with higher viral load, especially in co-occurrence of G142D [20]a. Also, it might confer adaptative advantages if combined with E484Q [21]a;
del142-144	N3 loop in NTD	–	It might be related to vaccine breakthrough infection [166]
Y145D	N3 loop in NTD	–	It might be related to reduced neutralization of convalescent sera and loos of biding by ADI-56479 MAb to the mutant protein [171]
del211	NTD	–	No articles were found
L212I	NTD	B.1.1.33 [172]	Reported in a case study 12 days after administration of convalescent plasma [173]
ins214EPE	–	–	Present in 86,3% of the Omicron cases (of a 131 sequence pool) [25]a Might have occurred because of template switching during viral co-infection or from prevalent templates in the human genome, such as transcripts expressed in alveolar cells or enterocytes [26]a - Structural: decreased protein stability − 0.71 [119]
G339D	RBD	Gamma [176]a	- Immune: creates a mild impact on various antibody-RBD complexes [147], and some evidence of immune escape from a subset of NAbs were also observed [177] - Structural: the Docking Energy of Omicron RBD-ACE2 for this mutation was − 507.06 and decreased protein stability − 1.16 [119]
S371L	RBD	–	- Immune: creates a mild impact on various antibody-RBD complexes [147], and some evidence of immune escape from a subset of NAbs were observed [177] - Structural: the Docking Energy of Omicron RBD-ACE2 for this mutation was − 549.34 and decreased protein stability − 0.22 [119]
S373P	RBD	Gamma, Lambda [178]	- Immune: reported to confer escape immunity elicited by mRNA vaccines [178, 179]. It creates a mild impact on various antibody-RBD complexes [147] - Structural: the Docking Energy of Omicron RBD-ACE2 for this mutation was − 541.87 and decreased protein stability − 0.53 [119]
S375F	RBD	–	- Immune: creates a mild impact on various antibody-RBD complexes because it lies far away from the biding interfaces of most known antibodies [147]. Also, seem to strengthen the biding with the H014 antibody present in some cocktails [180]. Despite that, some evidence of immune escape from a subset of NAbs were also observed[177] - Structure: the Docking Energy of Omicron RBD-ACE2 for this mutation was − 530.07 and decreased protein stability − 0.33 [119]
K417Nb	RBD	Delta plus [164] Multiple VOI and VOC by WHO [147]	- Immune: likely to scape vaccine-induced antibodies predicted by TopNetmAb model and together with E484A and Y505H, increased the evasion power of Omicron, compared with Delta variant, against 132 antibodies [147]. Other evidence of immune evasion was also reported [177, 181, 182] - Structural: reduced RBD stability and High ACE2 binding affinity [119, 183]. Part of an “interface-destabilizing” group and independently can strongly impact hACE2 biding [184]a

The mutations were searched in Scielo®, Google academic®, and CAPES Periodicals by the name of the mutation and the words “mutation” and “spike”. Only the articles that were specifically about the mutation were selected, along with other relevant papers that appeared during the reading

^aArticles still under peer review (preprints), please, analyze data with caution

^bMutations discussed in the text, also the research step was not done to these mutations, the data inserted in the table was a summarization of the data since an extensive work was already done and published about these mutations