Westendorf Kathryn, Žentelis Stefanie, Wang Lingshu, Foster Denisa, Vaillancourt Peter, Wiggin Matthew, Lovett Erica, van der Lee Robin, Hendle Jörg, Pustilnik Anna, Sauder J Michael, Kraft Lucas, Hwang Yuri, Siegel Robert W, Chen Jinbiao, Heinz Beverly A, Higgs Richard E, Kallewaard Nicole L, Jepson Kevin, Goya Rodrigo, Smith Maia A, Collins David W, Pellacani Davide, Xiang Ping, de Puyraimond Valentine, Ricicova Marketa, Devorkin Lindsay, Pritchard Caitlin, O'Neill Aoise, Dalal Kush, Panwar Pankaj, Dhupar Harveer, Garces Fabian A, Cohen Courtney A, Dye John M, Huie Kathleen E, Badger Catherine V, Kobasa Darwyn, Audet Jonathan, Freitas Joshua J, Hassanali Saleema, Hughes Ina, Munoz Luis, Palma Holly C, Ramamurthy Bharathi, Cross Robert W, Geisbert Thomas W, Menacherry Vineet, Lokugamage Kumari, Borisevich Viktoriya, Lanz Iliana, Anderson Lisa, Sipahimalani Payal, Corbett Kizzmekia S, Yang Eun Sung, Zhang Yi, Shi Wei, Zhou Tongqing, Choe Misook, Misasi John, Kwong Peter D, Sullivan Nancy J, Graham Barney S, Fernandez Tara L, Hansen Carl L, Falconer Ester, Mascola John R, Jones Bryan E, Barnhart Bryan C
bioRxiv. 2022 Mar 24:2021.04.30.442182. doi: 10.1101/2021.04.30.442182.
SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19.
LY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated.
LY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron), the BA.2 Omicron subvariant, and B.1.617.2 (Delta) variantsNo loss of potency against currently circulating variantsBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID databaseBreadth of neutralizing activity and potency supports clinical development.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中和单克隆抗体（mAb）在新冠病毒病（COVID-19）病程早期给药时可降低住院风险。然而，令人担忧的变异株的出现对一些已获授权的单克隆抗体的治疗应用产生了负面影响。我们使用高通量B细胞筛选流程，分离出一种高效的SARS-CoV-2刺突糖蛋白受体结合域（RBD）特异性抗体，称为LY-CoV1404（也称为贝博泰洛维单抗）。LY-CoV1404能有效中和真实的SARS-CoV-2病毒，包括原型毒株、B.1.1.7、B.1.351和B.1.617.2毒株。在假病毒中和研究中，LY-CoV1404对包括B.1.1.7、B.1.351、B.1.617.2、B.1.427/B.1.429、P.1、B.1.526、B.1.1.529和BA.2亚变体在内的多种变异株均保持高效中和活性，并能与具有多种潜在RBD突变（包括K417N、L452R、E484K和N501Y）的刺突蛋白结合。结构分析表明，除N439和N501外，LY-CoV1404表位的接触残基高度保守。值得注意的是，LY-CoV1404的结合和中和活性不受这些位置最常见突变（N439K和N501Y）的影响。对当前变异株中存在的氨基酸替换的反应广度、广泛而强效的中和活性以及相对保守的表位表明，LY-CoV1404有潜力成为治疗所有已知导致COVID-19的变异株的有效治疗药物。
LY-CoV1404是一种强效的SARS-CoV-2结合抗体，可中和所有已知的令人担忧的变异株，其表位很少发生突变。
LY-CoV1404能有效中和SARS-CoV-2真实病毒和已知的令人担忧的变异株，包括B.1.1.529（奥密克戎）、BA.2奥密克戎亚变体和B.1.617.2（德尔塔）变体
对当前正在传播的变异株效力无损失
在全球共享流感数据倡议组织（GISAID）数据库中，SARS-CoV-2 RBD上的结合表位很少发生突变
中和活性广度和效力支持临床开发
