Table 2.
Summary of the physical and functional alterations of S-protein due to notable amino acid substitutions.
| Mutation | Alterations in S-protein structure | Functional Consequences for VOC | Distribution Earliest/latest (frequency) |
Notes/references |
|---|---|---|---|---|
| D614G | • Substitution of aspartate to glycine at site
614. • Open conformity of S1 spike protein |
• Increased transmissibility • Increased vulnerability to host immune attack (speculated) • Higher nasal viral loads and correlates with the prevalence of anosmia |
1/3/2020 Switzerland (0.4) UK (0.19) France (0.15) Italy (0.11) |
69,70 |
| E484K | • Substitution of glutamate to lysine at site 484 • This change takes place in the receptor-binding motif on RBD |
• Increased ACE2 binding • Potential for escaping recognition from S-protein neutralizing antibodies. • Documented case of reinfection • Moderna and Pfizer have shown small but significant reduction in neutralization |
12/10/2020 Brazil (0.08) South Africa (0.06) 08/02/2021 Brazil (0.58) France (0.22) |
71,72 |
| N501Y | • Substitution from asparagine to tyrosine at position
501 • This change takes place at the RBD of the S-protein |
• Increase ACE2 binding due to increase duration in open
conformation. • Potential for escaping recognition from S-protein neutralizing antibodies. • >Moderna and Pfizer have shown small but significant reduction in neutralization. |
01/06/2020 Netherlands (0.01) 08/02/2021 UK (0.87) France (0.53) Australia (0.43) Brazil (0.42) |
72 –74 |
| HV69-70 del | • Deletion of histidine at site 69 and valine at site 70 in the
S1 domain of S-protein. • Predicted altered structure will be a ‘tucked in’ spike N-terminal domain |
• Potential for escaping recognition from S-protein neutralizing antibodies. The serum virus neutralization (SVN) assay showed reduced neutralization to human SARS-CoV-2 convalescent plasma. | 10/08/2020 Switzerland (0.04) Denmark (0.01) 08/02/2021 UK (0.87) Australia (0.45) France (0.36) Singapore (0.26) |
75,76 |
| P681H | • Substitution of proline to histidine at position 681 is immediately adjacent to the furin cleavage site between S1 and S2 in S-protein | • Enables increased cleavage activity by TMPRSS2. Therefore, increase SARS-CoV-2 entry | 12/10/2020 Nigeria (NA) UK (NA) |
64 |
RBD, receptor-binding domain; VOC, variants of concern.