The association of the S-protein of the SARS-CoV-2 beta coronavirus to ACE2 receptors of the human epithelial cells determines its contagiousness and pathogenicity. We computed the pH-dependent electric potential on the surface of the interacting globular proteins and pH-dependent Gibbs free energy at the association of the wild-type strain and the omicron variant. The calculated isoelectric points of the ACE2 receptor (pI 5.4) and the S-protein in trimeric form (pI 7.3, wild type), (pI 7.8, omicron variant), experimentally verified by isoelectric focusing, show that at pH 6–7, the S1–ACE2 association is conditioned by electrostatic attraction of the oppositely charged receptor and viral protein. The comparison of the local electrostatic potentials of the omicron variant and the wild-type strain shows that the point mutations alter the electrostatic potential in a relatively small area on the surface of the receptor-binding domain (RBD) of the S1 subunit. The appearance of seven charge-changing point mutations in RBD (equivalent to three additional positive charges) leads to a stronger S1–ACE2 association at pH 5.5 (typical for the respiratory tract) and a weaker one at pH 7.4 (characteristic of the blood plasma); this reveals the reason for the higher contagiousness but lower pathogenicity of the omicron variant in comparison to the wild-type strain.