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 CuInP₂S₆ (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.

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行引起的全球紧急情况只能通过有效且广泛的预防和治疗策略来解决，但两者都还不够。在这里，我们描述了一种超薄二维 CuInP ₂ S ₆ (CIPS) 纳米片作为抗 SARS-CoV-2 感染的新剂。CIPS对野生型 SARS-CoV-2 及其相关变体（包括 Delta 和 Omicron）的刺突蛋白的受体结合域表现出极高的选择性结合能力（解离常数 ( K _D ) < 1 pM），抑制病毒进入和感染血管紧张素转换酶 2 (ACE2) 携带细胞、人气道上皮类器官和人 ACE2 转基因小鼠。与 CIPS 结合后，病毒很快被巨噬细胞吞噬并消除，这表明 CIPS 可以成功地用于捕获并促进宿主消除病毒。因此，我们建议 CIPS 作为一种有前景的纳米药物，用于未来安全有效的抗 SARS-CoV-2 治疗，并作为去污剂和表面涂层材料来降低 SARS-CoV-2 感染性。