严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2，SARS-CoV-2)感染所致的2019冠状病毒病(coronavirus disease 2019，COVID-19)给人民的生命健康造成了严重的威胁，目前该病毒仍然在广泛传播，针对SARS-CoV-2有效的治疗方法仍有限，因此寻找广谱中和抗体阻断SARS-CoV-2感染具有重要的意义。本文成功表达并纯化了3株靶向SARS-CoV-2的受体结合结构域(receptor-binding domain，RBD)的人鼠嵌合抗体，并且检测了这几株抗体对多种SARS-CoV-2假病毒和活病毒的中和活性。本研究表明这3株抗体能特异性地中和SARS-CoV-2野生型假病毒，IC50分别为0.03 μg/mL、0.06 μg/mL、0.03 μg/mL。此外，这3株抗体对Alpha株假病毒、Delta株假病毒和Lambda株假病毒也具有广谱中和活性，并可以抑制SARS-CoV-2 Delta株活病毒的复制。机制研究表明，这些抗体可以阻断SARS-CoV-2的S蛋白介导的细胞-细胞融合，且RBD上的K417、E484和N501位点可能是其与这3株抗体结合的关键位点。

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a serious impact on people’s health and lives. At present, SARS-CoV-2 is still widely spread, but effective treatments for SARS-CoV-2 are still limited. Therefore, it is of great significance to find broad-spectrum neutralizing antibodies to block SARS-CoV-2 infection. In this study, we successfully expressed and purified three human-mouse chimeric antibodies targeting receptor-binding domain (RBD) of SARS-CoV-2, and then the neutralizing activities of these antibodies against a variety of SARS-CoV-2 pseudoviruses and authentic virus were tested. The results showed that these three antibodies could specifically neutralize SARS-CoV-2 wild-type pseudovirus, and the IC50 values were 0.03 μg/mL, 0.06 μg/mL and 0.03 μg/mL, respectively. Furthermore, these antibodies exhibited broad-spectrum neutralizing activity against Alpha, Delta and Lambda pseudoviruses, and could also inhibit the replication of SARS-CoV-2 Delta authentic virus. Mechanism studies showed that these antibodies could block cell-cell fusion mediated by SARS-CoV-2 S protein, and K417, E484 and N501 on receptor-binding domain (RBD) may be the key sites for binding with these three antibodies.