SARS-CoV spike proteins can compete for electrolytes in physiological fluids according to structure-based quantum-chemical calculations

Enrico Margiotta; Célia Fonseca Guerra

doi:10.1016/j.comptc.2021.113392

SARS-CoV spike proteins can compete for electrolytes in physiological fluids according to structure-based quantum-chemical calculations

Comput Theor Chem. 2021 Oct:1204:113392. doi: 10.1016/j.comptc.2021.113392. Epub 2021 Aug 5.

Authors

Enrico Margiotta^{1

2

3}, Célia Fonseca Guerra^{1

4}

Affiliations

¹ Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, the Netherlands.
² Department of Physics, University of Cagliari, Cittadella Universitaria S.P. Monserrato-Sestu Km 0.700, 09042 Monserrato (CA), Cagliari, Italy.
³ Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, United States.
⁴ Leiden Institute of Chemistry, Leiden University, PO Box 9502, NL-2300 RA Leiden, the Netherlands.

Abstract

The trimeric spike (S) glycoprotein is the trojan horse and the stronghold of the severe acute respiratory syndrome coronaviruses. Although several structures of the S-protein have been solved, a complete understanding of all its functions is still lacking. Our multi-approach study, based on the combination of structural experimental data and quantum-chemical DFT calculations, led to identify a sequestration site for sodium, potassium and chloride ions within the central cavity of both the SARS-CoV-1 and SARS-CoV-2 spike proteins. The same region was found as strictly conserved, even among the sequences of the bat-respective coronaviruses. Due to the prominent role of the main three electrolytes at many levels, and their possible implication in the molecular mechanisms of COVID-19 disease, our study can take the lead in important discoveries related to the SARS-CoV-2 biology, as well as in the design of novel effective therapeutic strategies.

Keywords: Central helix funnel; DFT; Ion binding; Physiological electrolytes; SARS-CoV; Spike protein.