Abstract
Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.
Highlights
SARS-CoV-2 is an enveloped positive-stranded RNA virus that depends on fusion of viral and target cell membranes to enter a host cell
Affinity for angiotensin converting enzyme 2 (ACE2) of the B.1.351 protein was lower than that of the B.1.1.7 variant. These results suggest that the mutations in the receptor-binding domain (RBD) of the B.1.1.7 variant (N501Y) enhance receptor recognition, while the additional mutations in the B.1.351 variant (K417N and E484K) reduce ACE2 affinity to a level close to that of the G614 protein, consistent with the previous data (36, 37)
In the B.1.1.7 virus, mutations A570D and S982A lead to an outward shift of the CTD1, thereby relaxing the FPPR and 630 loop, which help retain the RBD in its “down” position in the parental strain
Summary
SARS-CoV-2 is an enveloped positive-stranded RNA virus that depends on fusion of viral and target cell membranes to enter a host cell. We have previously identified two structural elements—the FPPR (fusion peptide proximal region) and 630 loop, which appear to modulate the S protein stability, as well as the RBD conformation and the receptor accessibility (22, 28). These results suggest that the mutations in the RBD of the B.1.1.7 variant (N501Y) enhance receptor recognition, while the additional mutations in the B.1.351 variant (K417N and E484K) reduce ACE2 affinity to a level close to that of the G614 protein, consistent with the previous data (36, 37).
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