Result: The amino acid changes in the spike protein, especially the aforementioned E484K, K417N, and N501Y have recently been reported to affect the neutralizing efficacy of the antibodies.
Result: The three B.1.351 variant substitutions E484K, K417N, and N501Y are in the groove of the RBD-ACE2 interaction domain.
Discussion: The critical amino acid changes linked to escape from humoral immunity in the B.1.351 variant appear to be K417N, E484K, and N501Y.
Evolution, correlation, structural impact and dynamics of emerging SARS-CoV-2 variants.
PMID: 34188776
2021
Computational and structural biotechnology journal
Abstract: However, reported greater binding affinity of N501Y Spike with ACE2 does not seem to be entirely due to increased hydrophobic interactions, given that Spike mutation R417T in P.1 or K417N in B.1.351 results in the loss of a salt-bridge interaction between ACE2 and S-RBD.
Abstract: Structural analysis indicated that the N501Y mutation may increase hydrophobic interactions at the ACE2/Spike interface.
Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.
Abstract: Importantly, LCB1v1.3 protected in vivo against a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions.
Discussion: Based on the cryoelectron microscopy (cryo-EM) structure of the parent LCB1 binder in complex with SARS-CoV-2 RBD, only the N501Y mutation is expected to affect binding.
Discussion: Because structural data suggested that the N501Y mutation might affect LCB1 binding, we tested LCB1v1.3 against a virus encoding this mutation in vivo.
Discussion: In comparison, LCB1v1.3 showed efficacy against historical (WA1/2020) and emerging (B.1.1.7 and E484K/N501Y/D614G) S
SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2.
Discussion: However, recent expansion of B.1.526, a lineage also featuring E484K but without N501Y in New York City, suggests that this fitness loss may be overcome by other, yet uncharacterized, changes in the virus as well.
Discussion: In fact, the B.1.351 RBD, which carries N501Y and E484K (as well as N417K) showed binding to hACE2 that was similar to wild-type RBD.
Discussion: Interestingly, Discussion: Interestingly, binding of convalescent sera to the N501Y RBD was also increased, suggesting that changes that increase affinity for the receptor may also increase affinity of a set of antibodies that may mimic the receptor.
A Unique SARS-CoV-2 Spike Protein P681H Variant Detected in Israel.
Introduction: Mutations in the SARS-CoV-2 genome affecting the S protein have emerged in numerous differentially-reported variants, such as the N501Y mutation that is shared by the currently known VOCs, B.1.1.7, B.1.351, and P.1, and which increase the affinity of the S protein to its receptor binding domain (RBD).
SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence.
Introduction: The major changes are the mutation N501Y in the receptor-binding domain (RBD); the deletion 69-70 which may increase transmissibility and produces a false negative in certain RT-PCR-based diagnostic assays; and the mutation P681H, next to the furin cleavage site, that could impact antigenicity and enhance viral infectivity.
Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?
Introduction: A combination of del H69/V70 and N501Y was shown to increase infectivity in vitro.
Introduction: Five mutations are located within NTD (L18F, T20N, P26S, D138Y, R190S), three in RBD (K417T, E484K, N501Y), two in the C-terminal domain of S1 and near the furin cleavage site (D614G, H655Y), and one in S2 (T1027I) (Figure 3).
Introduction: However, a combination of K417N and N501Y was shown to enhance the binding with ACE2 and reduce binding with a
Anti-SARS-CoV-2 Vaccines and Monoclonal Antibodies Facing Viral Variants.
Introduction: However, an absence of neutralization reduction was observed in other monoclonal antibodies in the case of Wash SA-B.1351 compared to the
Introduction: analyzed the impact of the neutralization of several mAbs on a panel of variants, including an authentic chimeric variant named Wash SA B.13 51, which contains the 20H/501Y.V2 Spike gene with other additional mutations (D80A, 242-244 del, R246I, K417N, E484K, N501Y, D614G and A701V), in addition to a panel of isogenic recombinant mutant variants (69-70 Del, K417N, E484K, N501Y, and/or D614G).
A Comprehensive Molecular Epidemiological Analysis of SARS-CoV-2 Infection in Cyprus from April 2020 to January 2021: Evidence of a Highly Polyphyletic and Evolving Epidemic.
Introduction: Furthermore, mutations/deletions in the S-protein, such as L18F, DeltaH69/V70, S898F, DeltaY144, S162G, A222V, N439K, N501Y, A570D, D614G, P681H, S982A and D1118H, were discovered in the lineages identified in this study and have phenotypic and antigenic implications that may impact the spread of the virus, as well as the efficiency of current vaccines and diagnostic tests.
Discussion: The following mutations within the S protein have been reported in this lineage: