Insights into SARS-CoV-2's Mutations for Evading Human Antibodies: Sacrifice and Survival.
PMID: 33834772
2022
Journal of medicinal chemistry
Abstract: It is known that N501Y and E484K can enhance binding between the coronavirus receptor domain (RBD) and human ACE2.
Abstract: The highly infectious SARS-CoV-2 variant B.1.351 that first emerged in South Africa with triple mutations (N501Y, K417N, and E484K) is globally worrisome.
Introduction: In addition to the N501Y mutation, the South Africa and Brazil variants also contain the K417N and E484K mutations.
Introduction: Recent studies showed that the E484K mutation not only can enhance RBD-ACE2 binding but also can help the virus escape the therapeutically relevant mAbs.
D
Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination.
Discussion: A regional variant was detected with increased prevalence in February 2021 that combined S: P681H and S: E484K.
Discussion: Notably, the circulation of variants carrying S: E484K has been temporary and the prevalence of this change remains sparse.
Discussion: Our data show that variants that carried S: E484K showed temporary circulation, in contrast to variants with S: P681H.
Discussion: The S: E484K variants B.1.351 and P1, however, were more successful in South Africa and South America, respectively.
Molecular definition of severe acute respiratory syndrome coronavirus 2 receptor-binding domain mutations: Receptor affinity versus neutralization of receptor interaction.
Abstract: In contrast, single mutation E484K had almost no impact on the binding kinetics, but essentially abolished recognition of RBD by convalescent sera.
Abstract: Interestingly, combining mutations E484K, K417N, and N501Y resulted in a RBD with both features: enhanced receptor binding and abolished immune recognition.
Abstract: METHODS: We produced wild type RBD, RBD with single mutations (E484K, K417N, or N501Y) or with all three mutations combined and tested their binding to ACE2 by biolayer interferometry (BLI).
Result:
Table: E484K
Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest (VOI) A.23.1 identified in Uganda.
Abstract: The A.23 viral lineage, characterized by three spike mutations F157L, V367F and Q613H, was first identified in COVID-19 cases from a Ugandan prison in July 2020, and then was identified in the general population with additional spike mutations (
Introduction: This lineage then spilled into the general population adding additional spike mutations (R102I, L141F, E484K and P681R, as well as in nsp6, ORF8 and ORF9:to comprise lineage A.23.1:by September 2020.
Abstract: In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y.
Post-Vaccination Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections and Incidence of the Presumptive B.1.427/B.1.429 Variant Among Healthcare Personnel at a Northern California Academic Medical Center.
Result: Anti-RBD IgG ELISA shows that antibodies induced by infection with wild-type Wuhan SARS-CoV-2 fail to recognize the RBD mutants L452R/E484Q (variant B.1.617) and E484K (variants P.1 and B.1.351), while recognition of RBDN440K is unaltered.
Result: As shown previously, vaccination induces antibodies with broader specificity than viral infection, resulting in antibodies that showed reduced binding to RBD carrying mutation E484K while all other RBDs, including the Indian variants of concern were recognized well by the vaccine-induced immune sera (Figure 3C).
Result: Binding kinetics of RBD mutants to ACE2 show increased af
Emergence of the E484K Mutation in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Lineage B.1.1.345 in Upstate New York.
Abstract: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.345 variant carrying the E484K mutation was detected in 4 patients with no apparent epidemiological association from a hospital network in upstate New York.
Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination.
Result: including N501Y in both Alpha and Beta, E484K in Eta and Beta, K417N in Beta, and L452R and T478K only in Delta.
Discussion: Amino acid changes in spike proteins of variants contribute to immune evasion, and it has been suggested that N501Y is associated with increased infectivity, whereas L452R, T478K, and E484K with K417N reduce the interaction of neutralizing antibodies with RBD.
Discussion: However, Eta with slightly reduced neutralization results has solely an E484K substitution, indicating that the
ViMRT
SARS_CoV_2 mutation literature information.
PMID: 
2022
Journal of medicinal chemistry
