Fig. 1: Sequence variation in spike glycoprotein.

The open reading frame encoding spike (S) is illustrated, with the position of key features of processing and function indicated to approximate scale (residue number indicated above). During co-translational translocation to the endoplasmic reticulum (ER), the short leader peptide (LP) is proteolytically removed. Following folding, trimer assembly and glycosylation in the ER and Golgi, the trans-Golgi localized protease, furin, cleaves the boundary between the S1 and S2 polypeptides. Following binding of the receptor-binding domain (RBD, cyan) to ACE2 on host cells, cell-surface TMPRSS2 proteolytically cleaves the S2’ site, facilitating conformational changes to spike that result in fusion of the virus envelope with the plasma membrane. Variant residue positions are indicated below, and their approximate location on the S polypeptide is indicated. Residue identities are shown at each of these positions for a prototype lineage B isolate, and at each position in four lineages of interest, B.1.1.7 (α—Alpha), B.1.351 (β—Beta), P.1 (γ—Gamma) and B.1.617 (δ—Delta), at which the respective lineage differs from prototype. Δ indicates deletion of one or more residues. Note, there are lineage-defining substitutions outside RBD, in the N-terminal domain (NTD) and C-terminal domain (CTD) of S1 (dark blue), and in S2 (tan). These may include changes that directly or indirectly affect antibody-mediated neutralization or cellular immunity, by loss or altered dynamics of epitope, respectively.