Omicron: a drug developer’s perspective

Figures & data

Table 1. Annotation of the Omicron spike mutations.

Omicron (B.1.1.529) spike mutations		Annotation	Mutation presence & prevalence up to 30 November 2021	Mutation impact
Spike protein N-terminal domain (NTD)	A67V	Evaded nAb binding [4].	Eta	Immune evasion
	ΔH69-V70	In the N2 neutralizing epitope and assiciated with convalescent plasma escape. Evaded nAb binding [4].	Alpha, Eta & C.36.3-related	Immune evasion
	T95I	Alters the N3 epitope topography.	B.1.1.318-related & Iota	Immune evasion
	G142D, Δ143-145	In the N3 neutralizing epitope. Abolished binding by nAbs [3,4].	Alpha, Eta & C.1.2.; Mu (Y144S, Y145N)	Immune evasion
	Δ211/L212I, ins214EPE	In a predicted HLA class II epitope [5].		Immune evasion?
Spike receptor binding domain (RBD) & Receptor binding module (RBM)	G339D	In the classes 3 & 4 neutralizing epitope [6].	Detected in 469 sequences	Immune evasion?
	S371L, S373P, S375F	In the classes 3 & 4 neutralizing epitope [6].	S:371L: in 11 sequences. S373P: in 322 sequences. S375F: in 208 sequences.	Immune evasine?
	K417N	In the class 1 neutralizing epitope and evaded nAbs [6,7].	Beta; Gamma (K417T). Delta (AY.2)	Evasion of both humoral & cellular immunity
	N440K	In the class 3 neutralizing epitope and may escape nAbs [6,7].	Detected in 8,153 sequences	Immune evasion
	G446S	In the class 3 neutralizing epitope [5,6]. May evade some nAbs [7].	Detected in 671 sequences	Immune evasion
	S477N	In the class 1 neutralizing epitope [6]. Strongly resistant to a panel of nAbs [19].	Iota; Detected in 70,964 sequences	Immune evasion
	T478K	May evade some nAbs [19].	Delta.	?
	E484A	In the class 2 neutralizing epitope [7]. Strongly resistant to a panel of nAbs [7]. Multiple E484 mutations conferred resistance to convalescent sera [19].	E484K: Beta, Gamma, Iota, Mu, Eta, & Theta; E484Q: Kappa	Immune evasion
	Q493R	In the class 2 neutralizing epitope and may escape nAbs.	Detected in 145 sequences	Immune evasion
	G496S	May be partially resistant to nAbs.	Detected in 480 sequences	?
	Q498R	At ACE2 interphase. May increase ACE2 affinity to low pM-level when combined with N501Y, E484K, & S477N [13].	Detected in 113 sequences, 22 sequences carry Q498R & N501Y dual mutations.	Enhanced infectivity & Immune evasion
	N501Y	At ACE2 interphase; In class 1 neutralizing epitope and may evade some nAbs.	Alpha, Beta, Gamma, Mu	Enhanced infectivity & Immune evasion
	Y505H	In the class 1 neutralizing epitope.	Detected in 130 sequences	Immune evasion
Spike protein C-terminal segment	T547K		Detected in 607 sequences	?
	D614G	Decreased HLA class I binding. Increases infectivity and transmissibility [20].	Alpha, Beta, Gamma, Delta, Kappa, Lambda, Eta, Iota, Mu, Theta, C.1.2, B.1.1.318, & C36.3	Enhanced infectivity & Evasion of both humoral & cellular immunity
	H655Y	Adjacent to the S1/S2 furin cleavage site	Gamma, C.1.2	Enhanced infectivity
	N679K	Adjacent to the S1/S2 furin cleavage site	C.1.2	Enhanced infectivity
	P681H	Adjacent to the S1/S2 furin cleavage site & in a HLA-B7 epitope [20]. Type I IFN resistance.	Alpha, Mu; P681R: Delta, Kappa	Enhanced infectivity. Evasion of innate & cellular immunity
	N764K		Detected in 345 sequences	?
	D796Y	In an HLA-II epitope [4]. In a epitope recognized by convalescent sera [11].	Detected in 4053 sequences	Immune evasion?
	N856K	Adjacent to the fusion-peptide triad (K835, Y837 & K854) that interact with D614.	Detected in 57 sequences	Altered infectivity?
	Q954H	In a predicted HLA class II epitope [5].	Detected in 30 sequences	Immune evasion?
	N969K	In a predicted HLA class II epitope [5].	Detected in 63 sequences	Immune evasion?
	L981F		Detected in 40 sequences	?

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