The coronavirus induced disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide threat to human lives, and neutralizing antibodies present a great therapeutic potential in curing affected patients. We purified more than one thousand memory B cells specific to SARS-CoV-2 S1 or RBD (receptor binding domain) antigens from 11 convalescent COVID-19 patients, and a total of 729 naturally paired heavy and light chain fragments were obtained by single B cell cloning technology. Among these, 178 recombinant monoclonal antibodies were tested positive for antigen binding, and the top 13 binders with Kd below 0.5 nM are all RBD binders. Importantly, all these 13 antibodies could block pseudoviral entry into HEK293T cells overexpressing ACE2, with the best ones showing IC50s around 2-3 nM. We further identified 8 neutralizing antibodies against authentic virus with IC50s within 10 nM. Among these, 414-1 blocked authentic viral entry at IC50 of 1.75 nM and in combination with 105-38 could achieve IC50 as low as 0.45 nM. Meanwhile, we also found that 3 antibodies could cross-react with the SARS-CoV spike protein. Altogether, our study provided a panel of potent human neutralizing antibodies for COVID19 as therapeutics candidates for further development.

中文翻译：

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人类IgG中和单克隆抗体阻断SARS-CoV-2感染

由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）引起的冠状病毒诱发的疾病19（COVID-19）已成为对人类生命的全球性威胁，中和抗体在治愈受感染患者方面具有巨大的治疗潜力。我们从11名恢复期的COVID-19患者中纯化了1000多种针对SARS-CoV-2 S1或RBD（受体结合结构域）抗原的特异性记忆B细胞，并且通过单个B获得了总共729个自然配对的重链和轻链片段细胞克隆技术。其中，测试了178个重组单克隆抗体的抗原结合呈阳性，且Kd值低于0.5 nM的前13种结合剂均为RBD结合剂。重要的是，所有这13种抗体都可以阻止假病毒进入过表达ACE2的HEK293T细胞，最好的抗体显示IC50约为2-3 nM。我们进一步鉴定了8种中和抗体，可对抗10nM以内的IC50的真实病毒。其中414-1以1.75 nM的IC50阻断了真正的病毒进入，并与105-38结合使用可将IC50降低至0.45 nM。同时，我们还发现3种抗体可以与SARS-CoV峰值蛋白发生交叉反应。总之，我们的研究提供了一组针对COVID19的有效人类中和抗体，作为进一步开发的治疗候选药物。