Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383, Wrocław, Poland.
School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
Chemistry. 2023 Oct 2;29(55):e202301530. doi: 10.1002/chem.202301530. Epub 2023 Aug 31.
The 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-NH (L1) and Ac-WSHPQFEK-NH (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.
新型冠状病毒肺炎疫情对全球健康造成了毁灭性影响，凸显了深入了解 SARS-CoV-2 病毒如何损害肺部以开发有效治疗方法的必要性。最近的研究表明，COVID-19 患者的各种生物分子经历严重的氧化损伤。我们提出，SARS-CoV-2 感染中活性氧（ROS）的过度产生涉及铜离子与病毒刺突蛋白之间的相互作用。我们测试了两个来自武汉株和β变体的刺突蛋白的肽片段 Ac-ELDKYFKNH-NH（L1）和 Ac-WSHPQFEK-NH（L2），发现它们结合 Cu(II) 离子并在肺 pH 值下形成三氮络合物。我们的研究表明，这些络合物引发 ROS 的过度产生，ROS 可以破坏两条 DNA 链并将 DNA 转化为线性形式。使用 A549 细胞，我们证明 ROS 的过度产生发生在线粒体中，而不是细胞质中。我们的发现强调了铜离子与病毒刺突蛋白相互作用在肺损伤发展中的重要性，并可能有助于治疗程序的开发。
