Nanoparticles insert a three dimensional cavity structure of proteins for function inhibition: The Case of CeO2 and SARS-CoV-2

作     者：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 Bastus, Neus G. Himly, Martin Wang, Liming Liu, Feng-Liang Zheng, Yong-Tang Puntes, Victor Li, Yang 

作者机构：Chinese Acad Sci Shenzhen Inst Adv Technol Lab Inflammat & Vaccines Shenzhen 518055 Guangdong Peoples R China Chinese Acad Sci Lab Immunol & Nanomed Shenzhen 518055 Guangdong Peoples R China Chinese Acad Sci Shenzhen Inst Adv Technol China Italy Joint Lab Pharmacobiotechnol Med Immun Shenzhen 518055 Guangdong Peoples R China Chinese Acad Sci Shenzhen Inst Adv Technol Res Ctr Human Tissues & Organs Degenerat Shenzhen 518055 Guangdong Peoples R China Chinese Acad Sci Ctr Biosafety Mega Sci Kunming Inst ZoolKey Lab Anim Models & Human Dis Key Lab Bioact Peptides Yunnan ProvKIZ CUHK Joint Kunming 650223 Peoples R China Paris Lodron Univ Salzburg Dept Biosci & Med Biol A-5020 Salzburg Austria Loyola Univ Chicago Stritch Sch Med Dept Med Div HepatolProgram Expt & Theoret Modeling Maywood IL 60153 USA Southern Univ Sci & Technol Shenzhen 518055 Guangdong Peoples R China CSIC Instiut Catala Nanociencia Nanotecnol ICN2 Campus UAB Barcelona 08193 Spain Barcelona Inst Sci & Technol BIST Campus UAB Barcelona 08193 Spain CIBER Bioingn Biomat & Nanomed CIBER BBN Bellaterra Spain Vall dHebron Inst Recerca VHIR Barcelona 08035 Spain Chinese Acad Sci Inst High Energy Phys CAS Key Lab Biomed Effects Nanomat & Nanosafety Beijing 100049 Peoples R China Vall dHebron Inst Recerca VHIR Barcelona 08035 Spain Inst Catalana Recerca i Estudis Avancats ICREA Barcelona 08010 Spain 

出 版 物：《NANO TODAY》 (Nano Today)

年 卷 期：2024年第55卷

核心收录：

学科分类：07[理学] 070203[理学-原子与分子物理] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 0702[理学-物理学] 

基　　金：National Key R & D Program of China [2021YFE0113000, 2022YFC2303700] National Natural Science Foundation of China [82261138630, 32171390, 32201154, 51872318, 32371469, 31971322] Natural Science Foundation of Guangdong Province [2023A0505050123, 2023B1515020104, 2022A1515010549] International Partnership Program (IPP) of CAS [172644KYSB20210011] Key Collaborative Research Program of the Alliance of International Science Organizations [ANSO-CR-KP-2022-01] CAS President's International Fellowship Initiative [2020VBA0022] Austrian Academic Exchange Service (OeAD) [CN06/2021] SmartCERIALS project of the Austrian Research promotion Agency (FFG) 

主　　题：Protein corona Protein 3D Structure Selective binding protein SARS-CoV-2 Cerium oxide nanoparticles 

摘      要：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.