SARS-CoV-2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate?

Abstract

Lineage B.1.617+, also known as G/452R.V3 and now denoted by WHO with the Greek letters δ and κ, is a recently described SARS-CoV-2 variant under investigation first identified in October 2020 in India. As of May 2021, three sublineages labeled as B.1.617.1 (κ), B.1.617.2 (δ), and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R, and P681R. Here, we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the receptor-binding domain (RBD) of the spike protein. Enhanced RBD-EP is particularly noticeable in the B.1.617.2 (δ) sublineage, which shows multiple replacements of neutral or negatively charged amino acids with positively charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+ RBD and the negatively charged ACE2, thus conferring a potential increase in the virus transmission.

Keywords: B.1.617 δ and κ variants; SARS-CoV-2; electrostatics potential changes.

Figure 1

Comparison between the wild‐type and variant spike receptor‐binding domains (RBDs). Protein surface is colored according to the electrostatic potential. Color scale ranges from −5 kT/e (red) to +5 kT/e (blue) as reported by the bar under the wild‐type RBD. Position of the mutant sites is indicated by a circle and an attached label. Red arrows mark the area of increased positive potential in the RBD Indian variants

Figure 2

Ribbon model of the interface between ACE2 (deep teal) and receptor‐binding domain (RBD) (orange). Sidechains of relevant residues are displayed as stick models and labeled. The two mutations at the RBD sites 417 and 484 have been simultaneously displayed