literature

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.

PMID: 34016740 2021 Science (New York, N.Y.)

Introduction: Among 585,054 SARS-CoV-2 genome sequences in the GISAID database (March 5, 2021), about 95% of K417N/T mutations occur with N501Y, despite N501Y being present in only 21% of all analyzed sequences.

Introduction: Binding and neutralization of four and five antibodies out of the 17 tested were abolished by K417N and E484K, respectively.

Introduction: Consistently, K417N/T mutat

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.

PMID: 34021265 2021 Cell research

Abstract: Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause.

Abstract: VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions.

Introduction: 501Y.V2 is associated with multiple S mutations, which could be divided into two main subsets, one is clustered in NTD (L18F,

PMID: 34023401 2021 Journal of molecular biology

Result: The K417N mutation is expected to reduce affinity as replacement of the lysine with a shorter asparagine (in B.1.351, or threonine in P.1) will disrupt the salt-bridge across the interface (Figure S1(E) and (F)).

Result: The combination of all three mutations, as present in strain B.1.351 (first identified in South Africa), is predominantly additive and results in a 2.4-fold less stable complex than for N501Y alone due to the effect of K417N, but still 3-fold more stable than with wild type RBD (Figure 1(F), table 1).

Result: The single K417N mutation destabilizes the interaction with hACE2 4-fold through a combination of slower binding and faster dissociation (Figure 1(F), table 1).

Implications of the Novel Mutations in the SARS-CoV-2 Genome for Transmission, Disease Severity, and the Vaccine Development.

PMID: 34026780 2021 Frontiers in medicine

Introduction: E484K and K417N mutation can reduce the binding of antibodies to the virus.

Introduction: Additionally, the South African variant carries E484K and K417N mutations that can reduce the binding of antibodies to the virus.

Introduction: Both the B.1.351 variant and the B.1.1.28 variant have N501Y, E484K, and K417N mutations in the spike protein.

Molecular dynamics analysis of N-acetyl-D-glucosamine against specific SARS-CoV-2's pathogenicity factors.

PMID: 34043733 2021 PloS one

Discussion: The findings of Cheng and colleagues provided a higher affinity to the human ACE2 receptor, among the mutations, are the N501Y, K417N, and E484K mutations.

E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil.

PMID: 34044192 2021 Infection, genetics and evolution

Introduction: The second lineage probably emerged in South Africa in August 2020 and harbors three mutations in RBD: K417N, E484K, and N501Y.

Discussion: It was structurally demonstrated that, at least in combination with K417N and N501Y, the substitution has profound impact in shifting the main site of contact between viral RBD and hACE-2 residues.

Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective.

PMID: 34049205 2021 Biochemical and biophysical research communications

Abstract: The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, whi

Method: Molecular Dynamic Simulation (MDS) on the spike RBD WT and mutated (K417 N, E484K, and N501Y) is performed using Nanoscale molecular dynamics software (NAMD) version 2.13.

Method: The PyMOL V2.2.2 software was utilized to prepare the corresponding RBD mutations (K417 N, E484K, and N501Y) found in SARS-CoV-2 variants 501.V2 and B.1.1.248.

Convalescent-Phase Sera and Vaccine-Elicited Antibodies Largely Maintain Neutralizing Titer against Global SARS-CoV-2 Variant Spikes.

PMID: 34060334 2021 mBio

Result: Analysis of the single mutations of B.1.351 showed that the escape from REGN10933 was due to K417N and E484K, each of which on its own was sufficient.

Result: Analysis of the single point mutations showed that the decrease in neutralizing titers was caused by E484K, K417N, and Y453F mutations.

Discussion: The escape was the result of the K417N and E484K mutations in the RBD, either of which prevents neutralization, consistent with the findings of Wang et al.

The Spike of Concern-The Novel Variants of SARS-CoV-2.

PMID: 34071984 2021 Viruses

Introduction: Both the K417T and K417N mutations abolish this bond and are therefore predicted to have a lower hAce2 affinity while helping to evade neutralizing antibodies.

Introduction: Its Spike protein shares the three RBD mutations at the key residues K417, E484, and N501 (K417N, E484K, N501Y) with the Brazilian P.1 strain (please note the K417 is replaced by an asparagine in B.1.351 but a threonine in P.1) (Figure 2, Table 1).

Introduction: The main impact of the K417N mutation seems to be its ability to destabilize the RBD-down conformation, thereby increasing the propensity of the open configuration.

501Y.V2 and 501Y.V3 variants of SARS-CoV-2 lose binding to bamlanivimab in vitro.

PMID: 34074219 2021 mAbs

Abstract: We found that the mutations K417N, E484K, and

Introduction: However, this same N501Y mutation is also found in a variant (B.1.351, 20 H/501Y.V2) with mutations of K417N, E484K, and N501Y from South Africa and a variant (P1, 20 J/501Y.V3) with K417T, E484K, and N501Y from Brazil with additional mutations within the RBD.

Introduction: The two additional mutations, K417N/T and E484K, are also critical residues involved in the interactions between RBD and ACE2, as well as bamlanivimab.