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Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor.
Hristova, Svetlana H; Zhivkov, Alexandar M.
Afiliação
  • Hristova SH; Department of Medical Physics and Biophysics, Medical Faculty, Medical University-Sofia, Zdrave Str. 2, 1431 Sofia, Bulgaria.
  • Zhivkov AM; Institute of Physical Chemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 11, 1113 Sofia, Bulgaria.
Viruses ; 15(8)2023 08 17.
Article em En | MEDLINE | ID: mdl-37632094
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Enzima de Conversão de Angiotensina 2 / COVID-19 Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Enzima de Conversão de Angiotensina 2 / COVID-19 Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article