Abstract: Although vaccine-elicited neutralizing antibody titers are decreased similarly against the E406 mutant and the Delta or Epsilon variants, broadly neutralizing sarbecovirus mAbs, including a clinical mAb, inhibit the E406W spike mutant.
Method: The construct encoding the E406W Method: The wildtype, B.1.1.7, and E406W RBDs were produced by transfecting 25 mL of Expi293 cells at a density of 2.5 x 106 cells per mL with 25 mug of DNA using the ExpiFectamine 293 Transfection Kit.
Method: To produce the SARS-CoV-2 spike ectodomain containing the E406W mutation, 125 mL of Expi293 cells were grown to density of 2.5 x 106 cells per mL and transfected with 125 mug of DNA using PEI MAX diluted in Opti-MEM.
A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F.
Introduction: Unlike the allosteric disruption of RBD structure observed in the case of the E406W mutation that also lead to broad antibody escape, the S371 mutations did not impact ACE-2 binding and only slightly reduced monomeric RBD expression when assayed via yeast display.
Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.
Discussion: For example, a yeast screening experiment showed that the E406W mutation on RBD abolishes neutralization by both NAbs in the REGN-COV2 cocktail, although this residue does not directly interact with either of them.
Convalescent-Phase Sera and Vaccine-Elicited Antibodies Largely Maintain Neutralizing Titer against Global SARS-CoV-2 Variant Spikes.
Discussion: A single mutation, E406W, allowed escape from both antibodies, although the residue is not located within the epitope bound by either antibody.
Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.
Discussion: The antigenic effect of key RBD mutations against the REGN-COV2 cocktail (REGN10933 and REGN10987) showed N439K and K444R variants escaped neutralization only by REGN10987, while E406W escaped both individual REGN-COV2 antibodies and the cocktail.
Characterization of a Novel ACE2-Based Therapeutic with Enhanced Rather than Reduced Activity against SARS-CoV-2 Variants.
Discussion: While not yet present in naturally occurring variants, the single amino acid mutation E406W has recently been shown to be able to escape both antibodies in the REGN-COV2 cocktail, further highlighting the weakness of the MAb approach.
Analysis of Immune Escape Variants from Antibody-Based Therapeutics against COVID-19: A Systematic Review.
PMID: 35008446
2021
International journal of molecular sciences
Discussion: E406W mutation, which causes resistance to REGN-COV-2, has never been reported in GISAID, and other E406 mutations remain exceedingly rare (worldwide, 318 cases of E406Q, 41 cases of E406D, and 2 cases each from USA for E406G, E406A, E406K, and 1 case of E406V out of 4,410,787 sequences deposited in GISAID as of 13 December 2021).
Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies.
SARS_CoV_2 mutation literature information.
PMID: 
2022
bioRxiv
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