Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion

Abstract

Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant's receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding β-loop-β motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.

Keywords: Antibody binding; Delta variant B.1.617.2; Immune escape; Molecular dynamics; SARS-CoV-2 variants.

Fig. 1

a) RBM showing the antiparallel β-strands. Residues R454 and D467 participating in ionic interactions in the Delta variant are shown as sticks. b) Hydrogen-bond network in the β-sheet region of the RBM for the WT and the Delta variant. c) % hydrogen bond occupancy obtained from the last 300 ns for the interactions in WT, B.1.1.7, B.1.351, and B.1.617.2. The sidechain interactions are denoted as SC.

Fig. 2

a) Reorientation of the disulfide bond. Right: changes in the dihedral angles for WT and the Delta variant. b) Distance between the center-of-mass between the two β-sheets (shown as the dotted line on the left).

Fig. 3

Frequency of occurrences of the RBD residues involved in hydrogen-bonding with Ab in 47 complexes from the Protein Data Bank.

Fig. 4

a) Amino acid residues involved in Ab-binding or ACE2-binding. b) The C_α-C_α distances between the residue pairs K458-A475 and N487-Q493 in WT. c) The C_α-C_α distances in the Delta variant.