Unravelling the Mystery of COVID‐19 Pathogenesis: Spike Protein and Cu Can Synergize to Trigger ROS Production

Author:

Katarzyna Lesiów Monika1ORCID,Witwicki Maciej1ORCID,Tan Nian Kee23,Graziotto Marcus Edward2,New Elizabeth Joy234

Affiliation:

1. Faculty of Chemistry University of Wrocław F. Joliot-Curie 14 50-383 Wrocław Poland

2. School of Chemistry The University of Sydney Sydney NSW 2006 Australia

3. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Sydney Sydney NSW 2006 Australia

4. Sydney Nano Institute The University of Sydney Sydney NSW 2006 Australia

Abstract

AbstractThe COVID‐19 pandemic has had a devastating impact on global health, highlighting the need to understand how the SARS‐CoV‐2 virus damages the lungs in order to develop effective treatments. Recent research has shown that patients with COVID‐19 experience severe oxidative damage to various biomolecules. We propose that the overproduction of reactive oxygen species (ROS) in SARS‐CoV‐2 infection involves an interaction between copper ions and the virus‘s spike protein. We tested two peptide fragments, Ac‐ELDKYFKNH‐NH2 (L1) and Ac‐WSHPQFEK‐NH2 (L2), derived from the spike protein of the Wuhan strain and the β variant, respectively, and found that they bind Cu(II) ions and form a three‐nitrogen complexes at lung pH. Our research demonstrates that these complexes trigger the overproduction of ROS, which can break both DNA strands and transform DNA into its linear form. Using A549 cells, we demonstrated that ROS overproduction occurs in the mitochondria, not in the cytoplasm. Our findings highlight the importance of the interaction between copper ions and the virus‘s spike protein in the development of lung damage and may aid in the development of therapeutic procedures.

Funder

Narodowe Centrum Nauki

Wroclawskie Centrum Sieciowo-Superkomputerowe, Politechnika Wroclawska

Publisher

Wiley

Subject

General Chemistry,Catalysis,Organic Chemistry

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