Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19). We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C135. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.

中文翻译：

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双特异性抗体中和循环中的 SARS-CoV-2 变体，防止逃逸并保护小鼠免受疾病侵害

针对 SARS-CoV-2 Spike (S) 受体结合域 (RBD) 的中和抗体是对抗 2019 年冠状病毒病 (COVID-19) 最有希望的方法之一。我们基于来自 COVID-19 恢复期供体 C121 和 C135 的两种抗体开发了一种双特异性 IgG1 样分子 (CoV-X2)。CoV-X2 同时结合 RBD 上的两个独立位点，并且与其亲本抗体不同，它阻止可检测到的 S 与病毒细胞受体血管紧张素转换酶 2 (ACE2) 结合。此外，CoV-X2 中和了 SARS-CoV-2 及其相关变体，以及亲本单克隆产生的逃逸突变体。在新型 SARS-CoV-2 感染肺部炎症动物模型中，CoV-X2 保护小鼠免受疾病侵害并抑制病毒逃逸。因此，