A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination

• Published in: Nature nanotechnology Vol. 17; no. 9; pp. 993 - 1003
• Main Authors: Zhang, Guofang, Cong, Yalin, Liu, Feng-Liang, Sun, Jiufeng, Zhang, Jiantian, Cao, Guoli, Zhou, Lingqiang, Yang, Wenjie, Song, Qingle, Wang, Fangjun, Liu, Ke, Qu, Jing, Wang, Jing, He, Min, Feng, Shun, Baimanov, Didar, Xu, Wei, Luo, Rong-Hua, Long, Xin-Yan, Liao, Shumin, Fan, Yunping, Li, Yu-Feng, Li, Bai, Shao, Ximing, Wang, Guocheng, Fang, Lijing, Wang, Huaiyu, Yu, Xue-Feng, Chang, Yan-Zhong, Zhao, Yuliang, Li, Liang, Yu, Peng, Zheng, Yong-Tang, Boraschi, Diana, Li, Hongchang, Chen, Chunying, Wang, Liming, Li, Yang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2022; Nature Publishing Group
• Subjects: 631/326/596/4130; 639/301/357/1018; ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Animal models; Animals; Biocompatibility; Chemistry and Materials Science; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Decontamination; Humans; Infections; Infectivity; Macrophages; Materials Science; Mice; Nanomaterials; Nanostructures - therapeutic use; Nanotechnology; Nanotechnology and Microengineering; Organoids; Pandemics; Peptidyl-dipeptidase A; Protein Binding; Proteins; Respiratory diseases; SARS-CoV-2; Selective binding; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Transgenic mice; Viral diseases; Viral infections; Viruses
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/s41565-022-01177-2

The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP 2 S 6 (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant ( K D ) < 1 pM) for the receptor binding domain of the spike protein of wild-type SARS-CoV-2 and its variants of concern, including Delta and Omicron, inhibiting virus entry and infection in angiotensin converting enzyme 2 (ACE2)-bearing cells, human airway epithelial organoids and human ACE2-transgenic mice. On association with CIPS, the virus is quickly phagocytosed and eliminated by macrophages, suggesting that CIPS could be successfully used to capture and facilitate virus elimination by the host. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, and as a decontamination agent and surface-coating material to reduce SARS-CoV-2 infectivity. While vaccines have curbed the COVID-19 pandemic, effective therapeutic treatments are few, and might be challenged by SARS-CoV-2 variants. A biocompatible, antiviral two-dimensional nanomaterial is now reported that firmly adsorbs the virus by interaction with the spike protein, inducing the conformational changes that lead to inhibition of viral infection in vitro and in animal models.