Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein

Alessio Pelucelli
ORCID logo ,
Massimiliano F Peana
* ORCID logo ,
Bartosz Orzeł
,
Elzbieta Gumienna-Kontecka
ORCID logo ,
Serenella Medici
ORCID logo ,
Maria Antonietta Zoroddu
ORCID logo
Version 1 : Received: 4 May 2023 / Approved: 4 May 2023 / Online: 4 May 2023 (08:09:22 CEST)

A peer-reviewed article of this Preprint also exists.

Pelucelli, A.; Peana, M.; Orzeł, B.; Piasta, K.; Gumienna-Kontecka, E.; Medici, S.; Zoroddu, M.A. Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein. Int. J. Mol. Sci. 2023, 24, 9202. Pelucelli, A.; Peana, M.; Orzeł, B.; Piasta, K.; Gumienna-Kontecka, E.; Medici, S.; Zoroddu, M.A. Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein. Int. J. Mol. Sci. 2023, 24, 9202.

Abstract

The spike protein (S) of SARS-CoV-2 has been shown to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor plays a critical role in the entry mechanism of SARS-CoV-2 virus. There are specific amino acids involved in the interaction between S protein and ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids that play a crucial role in the mechanism of interaction and recognition with the S protein are located in the C-terminal part which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates and histidine that could be targeted by metal ions. Zn2+ ion binds to the ACE2 receptor in its catalytic site and modulates its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such Zn2+, in the same region where it binds to the S protein could have a crucial impact in the mechanism of recognition and interaction of ACE2-S with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn2+, and also Cu2+ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques.

Keywords

ACE2; peptides; zinc complexes; copper complexes; metal interaction; potentiometry; spectroscopy; NMR

Subject

Chemistry and Materials Science, Applied Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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