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

Lineage B.1.617+, also known as G/452R.V3 and now denoted by WHO with the Greek letters delta and kappa, 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 (kappa), B.1.617.2 (delta), 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 (delta) 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.

Automated summary

Lineage B.1.617+, also known as G/452R.V3 and denoted by WHO as delta and kappa, is a newly described SARS-CoV-2 variant first identified in India in October 2020. Three sublineages, B.1.617.1 (kappa), B.1.617.2 (delta), and B.1.617.3, have been identified, with their potential impact on the current pandemic under investigation. This variant with 13 amino acid changes, including E484Q, L452R, and P681R, is characterized by a significant alteration in the surface electrostatic potential of the spike protein receptor-binding domain, particularly noticeable in the delta sublineage. The enhanced electrostatic potential change may facilitate the interaction between the B.1.617+ RBD and the ACE2 receptor, potentially increasing virus transmission.