1. Nanoparticles insert a three dimensional cavity structure of proteins for function inhibition: The Case of CeO2 and SARS-CoV-2
- Author
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National Natural Science Foundation of China, National Key Research and Development Program (China), Natural Science Foundation of Guangdong Province, Austrian Academy of Sciences, Austrian Research Promotion Agency, Zhang, Guofang, Wang, Xiaofeng, Wang, Guocheng, Suo, Xiaoman, Qiu, Yu, Luo, Rong-Hua, Liu, Yingnan, Li, Qi, Luo, Wenhe, Shi, Zhenzhen, Liu, Fangfang, Li, Zhongda, Qu, Jing, Li, Liang, Bastús, Neus G., Himly, Martin, Wang, Liming, Liu, Feng-Liang, Zheng, Yong-Tang, Puntes, Víctor F., Li, Yang, National Natural Science Foundation of China, National Key Research and Development Program (China), Natural Science Foundation of Guangdong Province, Austrian Academy of Sciences, Austrian Research Promotion Agency, Zhang, Guofang, Wang, Xiaofeng, Wang, Guocheng, Suo, Xiaoman, Qiu, Yu, Luo, Rong-Hua, Liu, Yingnan, Li, Qi, Luo, Wenhe, Shi, Zhenzhen, Liu, Fangfang, Li, Zhongda, Qu, Jing, Li, Liang, Bastús, Neus G., Himly, Martin, Wang, Liming, Liu, Feng-Liang, Zheng, Yong-Tang, Puntes, Víctor F., and Li, Yang
- Abstract
The selective interaction of nanomaterials with proteins for protein function suppression has been reported. However, whether the nanomaterials could be used to target a three-dimensional (3D) structure of proteins for the consequent function inhibition is not defined. When SARS-CoV-2 binds to the host cell surface ACE2 receptor, the spike protein trimer changes to an "Open State" which forms a 5 nm cavity structure, consequently exposing the receptor binding domain (RBD) for the following viral infection. We found that the 3 nm cerium oxide nanoparticles (CeO2@3) showed a better anti-SARS-CoV-2 effect than 30 nm cerium oxide nanoparticles (CeO2@30). We performed a series of experiments and demonstrated that the CeO2@3 could target the 5 nm spike protein trimer cavity and tightly bind with the RBD, thus effectively blocking the following virus-cell interaction and rendering CeO2@3 as an effective anti-viral agent. As all coronaviruses possess similar spike protein structures as homologous proteins, CeO2@3 can be used as a broad-sperm anti-coronavirus nanodrug candidate by targeting the spike protein 3D structure. This work, for the first time, demonstrated that rationally engineered inorganic nanomaterials can be used to specifically target a 3D structure of a certain protein for function inhibition, thus providing a novel methodological approach and paving the way for future molecular targeting nanodrug candidate design.
- Published
- 2024