Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 2020 Aug 15;205(4):915-922. doi: 10.4049/jimmunol.2000583. Epub 2020 Jun 26.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在全球范围内导致了数百万人感染和数十万人死亡。目前尚无针对 SARS-CoV-2 的广泛可用的许可治疗方法，这凸显了对有效干预措施的迫切需求。该病毒通过其三聚体刺突糖蛋白内的受体结合域与人类血管紧张素转换酶 2 的结合进入宿主细胞。在本文中，我们描述了一组针对受体结合域的鼠源单克隆抗体的产生和特性。一种单克隆抗体 2B04 以显著的效力（半最大抑制浓度<2ng/ml）在体外中和野生型 SARS-CoV-2。在 SARS-CoV-2 感染的小鼠模型中，2B04 可保护受感染的动物免受体重减轻、肺部病毒载量降低和阻止系统传播。因此，2B04 是一种有前途的有效抗病毒候选药物，可用于预防 SARS-CoV-2 感染。
