Electrostatic analysis of RBD of coronavirus mutants: from the wild-type strain to omicron variant

Title

Oral presentation

Description

Trifon Popov1, Svetlana Hristova1, Alexandar Zhivkov2
1Department of Medical Physics and Biophysics, Medical University – Sofia, Sofia, Bulgaria
2Institute of Physical Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria

Subject

The Coronavirus (SARS-CoV-2) binds to epithelial cells by electrostatic attractive forces between positively charged spike (S) proteins and negatively charged ACE2 receptors. Any point mutation, which alters the number and location of the positively charged amino groups (-NH3+) and negatively charged carboxyl groups (-COO–) in the receptor-binding domain (RBD) of the S1-subunit, changes the electrostatic potential and thus the association energy and contagiousness of the mutant. Our research consist of 5 stages: (1) selection of mutants with changed electrical charges in the RBD; (2) determination of the 3D coordinates and reconstruction of the S1-subunit structure; (3) computation of the electrostatic potential of the S1-subunit; (4) visualisation of the electrostatic potential on the surface of RBD; (5) calculation of the S1-ACE2 association energy. The results show that the positive net charge in RBD increases in the 4 most widespread coronavirus variants: +3 (wild type), +4 (β-variant), +5 (δ-variant) and +6 (ο-variant), which determine the increasing energy of association and contagiousness of these mutants. Our results also explain the higher contagiousness but lower pathogenicity of the omicron variant by pH dependence of its energy of association which is higher in the respiratory tract (pH 5) and lower in the blood vessels (pH 7.4). In conclusion, by computing the energy of S1-ACE2 association we can predict the contagiousness of newly emerged Coronavirus variants.
The study was supported by the National Research Fund (project KP-06-M49/1 - 2020).
Keywords: coronavirus, ACE2 receptor, RBD, association energy, contagiousness