The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), has caused a global pandemic. Antibodies are powerful biotherapeutics to fight viral infections; however, discovery of the most potent and broadly acting clones can be lengthy. Here, we used the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9E-14 M were achieved as a result of up to 10,000-fold potency enhancements. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and Ig-like in vivo bioavailability. This MULTi-specific, multi-Affinity antiBODY (Multabody; or MB) platform contributes a new class of medical countermeasures against COVID-19 and an efficient approach to rapidly deploy potent and broadly-acting therapeutics against infectious diseases of global health importance.

中文翻译：

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多价将SARS-CoV-2抗体转化为广泛和超强的中和剂

导致2019年冠状病毒病（COVID-19）的新型严重急性呼吸综合症冠状病毒2（SARS-CoV-2）引起了全球大流行。抗体是对抗病毒感染的强大生物疗法。但是，发现最有效和作用最广泛的克隆可能很漫长。在这里，我们使用人类载铁蛋白原蛋白作为模块亚基来驱动抗体片段的寡聚化，并将靶向SARS-CoV-2的抗体转化为异常有效的中和剂。使用该平台，由于增强了多达10,000倍的功效，因此获得的半最大抑制浓度（IC50）值低至9E-14M。三种不同抗体特异性和单个多价分子上的可结晶片段（Fc）结构域的组合赋予了克服病毒序列变异性的能力，同时具有出色的效价和Ig样的体内生物利用度。这个针对MULTi的多亲和力抗BODY（Multabody;或MB）平台提供了针对COVID-19的新型医学对策，并提供了一种有效的方法来快速部署有效且作用广泛的治疗剂，以应对具有全球健康重要性的传染病。