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Spike Protein Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

By Guofang Zhang, Yalin Cong, Guoli Cao, Liang Li, Peng Yu, Qingle Song, Ke Liu, Jing Qu, Jing Wang, Wei Xu, Shumin Liao, Yunping Fan, Yufeng Li, Guocheng Wang, Lijing Fang, Yanzhong Chang, Yuliang Zhao, Diana Boraschi, Hongchang Li, Chunying Chen, Liming Wang, Yang Li

Posted 14 Apr 2021
bioRxiv DOI: 10.1101/2021.04.13.439641

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

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