一种抗葡萄球菌肠毒素B超抗原的单克隆抗体可抑制新冠病毒进入。
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry .
作者信息
Cheng Mary Hongying, Porritt Rebecca A, Rivas Magali Noval, Krieger James M, Ozdemir Asli Beyza, Garcia Gustavo, Arumugaswami Vaithilingaraja, Fries Bettina C, Arditi Moshe, Bahar Ivet
机构信息
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
出版信息
bioRxiv. 2020 Nov 24:2020.11.24.395079. doi: 10.1101/2020.11.24.395079.
We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19, MIS-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin-like cleavage site.
我们最近在新冠病毒刺突蛋白的S1/S2切割位点附近发现了一个类似超抗原的基序，与葡萄球菌肠毒素B（SEB）相似，这可能解释了在儿童中观察到的多系统炎症综合征（MIS-C）以及重症新冠患者的细胞因子风暴。我们在此表明，一种抗SEB单克隆抗体（mAb）6D3能够结合该病毒基序，尤其是其PRRA插入序列，通过阻断宿主细胞蛋白酶TMPRSS2或弗林蛋白酶接近切割位点来抑制感染。6D3对弗林蛋白酶切割位点的高亲和力源于其重链互补决定区2（CDR2）的一个多酸性片段，这是与新冠病毒中和性单克隆抗体4A8共有的特征。6D3和4A8对该位点的亲和力表明它们作为治疗新冠、MIS-C或由具有弗林蛋白酶样切割位点的人类冠状病毒（HCoV）引起的普通感冒的潜在治疗用途。
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