SARS-CoV-2 infection—which involves both cell attachment and membrane fusion—relies on the angiotensin-converting enzyme 2 (ACE2) receptor, which is paradoxically found at low levels in the respiratory tract^1,2,3, suggesting that there may be additional mechanisms facilitating infection. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN and the sialic acid–binding immunoglobulin-like lectin 1 (SIGLEC1) function as attachment receptors by enhancing ACE2-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the amino-terminal domain or to the conserved site at the base of the receptor-binding domain, while poorly neutralizing infection of ACE2-overexpressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the receptor binding motif, while potently neutralizing infection of ACE2-overexpressing cells, poorly neutralize infection of cells expressing DC-SIGN or L-SIGN and trigger fusogenic rearrangement of the spike, promoting cell-to-cell fusion. Collectively, these findings identify a lectin-dependent pathway that enhances ACE2-dependent infection by SARS-CoV-2 and reveal distinct mechanisms of neutralization by different classes of spike-specific antibodies.

SARS-CoV-2 感染（涉及细胞附着和膜融合）​​依赖于血管紧张素转换酶 2 (ACE2) 受体，但矛盾的是，这种受体在呼吸道中含量较低^1,2,3，表明可能存在促进感染的其他机制。在这里，我们显示 C 型凝集素受体、DC-SIGN、L-SIGN 和唾液酸结合免疫球蛋白样凝集素 1 (SIGLEC1) 通过增强 ACE2 介导的感染和调节不同类别的中和活性来发挥附着受体的作用。刺突特异性抗体。针对氨基末端结构域或受体结合结构域底部保守位点的抗体，虽然对 ACE2 过表达细胞的感染中和作用较差，但有效阻断了凝集素促进的感染。相反，受体结合基序的抗体在有效中和过表达 ACE2 细胞的感染的同时，很难中和表达 DC-SIGN 或 L-SIGN 的细胞的感染，并引发刺突的融合重排，从而促进细胞间融合。