Table 1:
Spike protein amino acid substitutions associated with laboratory evidence of phenotypic impact.
| Amino acid substitution(s) | Spike-domain | VOC/VOI (Pango lineages) | Transmissibility | Immune escape | Miscellaneous | References |
|---|---|---|---|---|---|---|
| L18F | NTD | VOC Gamma (P.1) | Increased | Reduced neutralization; abrogated binding of NTD specific mAb |
https://doi.org/10.3390/v13030392, https://doi.org/10.1016/j.cell.2021.03.028 https://doi.org/10.1038/s41586-021-03398-2 https://www.science.org/doi/10.1126/scitranslmed.abj6824 |
|
| H69-V70del | NTD | VOC Alpha (B.1.1.7), VOI Eta (B.1.525), VOC Omicron (BA.1, BA.3, BA.4, BA.5) | Increased replication in upper airway of hamsters and primary human airway cells | Escape from NTD-specific antibodies | Increased infectivity associated with enhanced incorporation of cleaved spike into virions | https://doi.org/10.1016/j.celrep.2021.109292, https://doi.org/10.1038/s41586-021-04245-0 + DOI: 10.1126/science.abf6950 |
| D80A | NTD | VOC Beta (B.1.351) | Loss of recognition by T-cells, but overall T-cell response preserved; abrogated binding to NTD specific mAb | https://www.science.org/doi/10.1126/scitranslmed.abj6824, | ||
| T95I | NTD | VOI Iota (B.1.526), VOI Mu (B.1.621), VOC Omicron (BA.1) | Very minor effect | https://doi.org/10.1016/j.ebiom.2021.103626 | ||
| G142D | NTD | VOC Delta (B.1.617.2), VOI Kappa (B.1.617.1), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) |
Reduced neutralisation | https://www.science.org/doi/10.1126/science.abf6950, https://doi.org/10.1128/mBio.02473-21, https://dx.doi.org/10.1016%2Fj.cell.2021.03.028 | ||
| V143-Y145del | NTD | VOC Omicron (BA.1, BA.3) | Reduced neutralisation | https://www.science.org/doi/10.1126/science.abf6951, | ||
| Y144del | NTD | VOC Alpha (B.1.1.7), VOI Eta (B.1.525) | Reduced neutralisation | https://www.science.org/doi/10.1126/science.abf6952 | ||
| L242-A243del | NTD | VOC Beta (B.1.351) | Reduced neutralisation | https://doi.org/10.1038/s41591-021-01285-x | ||
| G339D | RBD | VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Escape from a subset of NAbs | Increased affinity for ACE-2 | https://doi.org/10.1038/s41586-021-04385-3,https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1 | |
| R346K | RBD | VOI Mu (B.1.621), VOC Omicron (BA.1.1) | Reduced neutralisation | https://www.nature.com/articles/s41586-022-04594-4_reference.pdf | ||
| S371L | RBD | VOC Omicron (BA.1) | Escape from a subset of NAbs | https://doi.org/10.1038/s41586-021-04385-3 | ||
| S375F | RBD | VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Escape from a subset of NAbs | https://www.nature.com/articles/s41586-021-04385-3#citeas | ||
| K417N | RBD | VOC Beta (B.1.351), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Reduced neutralisation | Decreased affinity for ACE-2 | https://doi.org/10.1038/s41586-021-04385-3, https://doi.org/10.1038/s41591-021-01294-w, https://doi.org/10.1101/2021.01.15.426911, | |
| K417T | RBD | VOC Gamma (P.1) | Reduced neutralisation | Decreased affinity for ACE-2 | https://doi.org/10.1038/s41586-021-04385-3 | |
| N440K | RBD | VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Escape from a subset of NAbs | Increased affinity for ACE-2 | https://doi.org/10.1038/s41586-021-04385-3, https://doi.org/10.1101/2020.11.30.405472, https://doi.org/10.7554/eLife.61312,https://doi.org/10.1126/science.abf4830,https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1 | |
| G446S | RBD | VOC Omicron (BA.1) | Reduced neutralisation | https://doi.org/10.1038/s41586-021-04385-3 | ||
| L452R | RBD | VOC Delta (B.1.617.2), VOI Epsilon (B.1.427, B.1.429), VOI Kappa (B.1.617.1) VOC Omicron (BA.4, BA.5) |
Reduced neutralisation | Increased affinity for ACE-2; increased infectivity | https://doi.org/10.1016/j.cell.2021.04.025,https://doi.org/10.1038/s41579-021-00573-0,https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1, https://doi.org/10.1016/j.chom.2021.06.006 | |
| L452Q | RBD | VOI Lambda (C.37) | Reduced neutralisation | Increased affinity for ACE-2; increased infectivity | https://doi.org/10.1080/22221751.2021.2008775,https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1,https://doi.org/10.1101/2021.07.02.450959 | |
| S477N | RBD | VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Reduced neutralisation | Increased affinity for ACE-2 | https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1,https://doi.org/10.1016/j.cell.2020.08.012, https://dx.doi.org/10.1016%2Fj.chom.2021.01.014 | |
| E484K | RBD | VOC Beta (B.1.351), VOC Gamma (P.1), VOI Zeta (P.2), VOI Eta (B.1.525), VOI Theta (P.3), VOI Mu (B.1.621) | Reduced neutralisation | Increased affinity for ACE-2 |
doi:10.1016/j.chom.2021.02.003 doi:10.1073/pnas.2103154118 doi:10.1016/j.chom.2021.01.014, https://doi.org/10.1038/s41586-021-03398-2 |
|
| E484A | RBD | VOC Omicron (BA.1, BA.2, BA.3) | Escape from a subset of Nabs; reduced neutralization by convalescent human sera and mAbs | doi:10.1016/j.chom.2021.01.014, https://doi.org/10.1038/s41586-021-04385-3, https://doi.org/10.1016/j.chom.2021.02.003 | ||
| F486V | RBD | VOC Omicron (BA.4, BA.5) | Escape from a subset of NAbs | Increased affinity for ACE-2 | https://doi.org/10.1038/s41467-021-24435-8, 10.1016/j.cell.2020.08.012 | |
| F490S | RBD | VOI Lambda (C.37) | Reduced neutralisation | https://doi.org/10.1016/j.chom.2021.01.014 + https://doi.org/10.1080/22221751.2021.2008775 | ||
| Q493R | RBD | VOC Omicron (BA.1, BA.2, BA.3) | Escape from a subset of NAbs | https://doi.org/10.1038/s41586-021-04385-3 | ||
| N501Y | RBD | VOC Alpha (B.1.1.7), VOC Beta (B.1.351), VOC Gamma (P.1), VOI Theta (P.3), VOI Mu (B.1.621), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Increased replication in upper airway of hamsters and primary human airway cells | Reduced neutralisation | Increased affinity for ACE-2 | https://doi.org/10.1016/j.cell.2021.02.042, https://doi.org/10.1038/s41586-021-03412-7, https://www.biorxiv.org/content/10.1101/2022.02.24.481899v1 |
| D614G | SD2 | VOC Alpha (B.1.1.7), VOC Beta (B.1.351), VOC Gamma (P.1), VOC Delta (B.1.617.2), VOI Epsilon (B.1.427, B.1.429) VOI Zeta (P.2), VOI Eta (B.1.525), Theta (P.3), VOI Iota (B.1.526), VOI Kappa (B.1.617.1), VOI Lambda (C.37), VOI Mu (B.1.621), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Increased infectivity in vitro; enhanced transmission in animal model; enhanced replication in upper respiratory tract | https://doi.org/10.1016/j.cell.2020.11.020, https://doi.org/10.1126/science.abe8499 | ||
| H655Y | Around S1/S2 site | VOC Gamma (P.1), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Increased transmissibility in vivo | Escape from a subset of NAbs | https://doi.org/10.1016/j.chom.2022.01.006, https://www.science.org/doi/10.1126/science.abd0831 | |
| P681H | Around S1/S2 site | VOC Alpha (B.1.1.7), VOI Theta (P.3), VOI Mu (B.1.621), VOC Omicron (BA.1, BA.2, BA.3, BA.4, BA.5) | Enhanced cleavage; viral entry or cell-to-cell spread not significantly impacted | https://doi.org/10.1016/j.isci.2021.103589 | ||
| P681R | Around S1/S2 site | VOC Delta (B.1.617.2), VOI Kappa (B.1.617.1) | Enhanced cleavage, significant resistance to several mAbs and vaccine elicited NAb | https://dx.doi.org/10.1101%2F2021.08.12.456173, https://doi.org/10.1038/s41586-021-04266-9 |
Abbreviations: mAbs – monoclonal antibodies; NAbs – neutralising antibodies. NTD – N-terminal domain; RBD – Receptor Binding Domain; ACE2 – Angiotensin converting enzyme 2