Hernandez Nancy E, Jankowski Wojciech, Frick Rahel, Kelow Simon P, Lubin Joseph H, Simhadri Vijaya, Adolf-Bryfogle Jared, Khare Sagar D, Dunbrack Roland L, Gray Jeffrey J, Sauna Zuben E
Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research U.S. FDA, Silver Spring, MD, USA.
Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Heliyon. 2023 Apr;9(4):e15032. doi: 10.1016/j.heliyon.2023.e15032. Epub 2023 Apr 3.
The human infectious disease COVID-19 caused by the SARS-CoV-2 virus has become a major threat to global public health. Developing a vaccine is the preferred prophylactic response to epidemics and pandemics. However, for individuals who have contracted the disease, the rapid design of antibodies that can target the SARS-CoV-2 virus fulfils a critical need. Further, discovering antibodies that bind multiple variants of SARS-CoV-2 can aid in the development of rapid antigen tests (RATs) which are critical for the identification and isolation of individuals currently carrying COVID-19. Here we provide a proof-of-concept study for the computational design of high-affinity antibodies that bind to multiple variants of the SARS-CoV-2 spike protein using RosettaAntibodyDesign (RAbD). Well characterized antibodies that bind with high affinity to the SARS-CoV-1 (but not SARS-CoV-2) spike protein were used as templates and re-designed to bind the SARS-CoV-2 spike protein with high affinity, resulting in a specificity switch. A panel of designed antibodies were experimentally validated. One design bound to a broad range of variants of concern including the Omicron, Delta, Wuhan, and South African spike protein variants.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒引起的人类传染病新型冠状病毒肺炎（COVID-19）已成为全球公共卫生的重大威胁。开发疫苗是应对流行病和大流行病的首选预防措施。然而，对于已感染该疾病的个体而言，快速设计能够靶向SARS-CoV-2病毒的抗体满足了一项关键需求。此外，发现能够结合SARS-CoV-2多种变体的抗体有助于开发快速抗原检测（RAT），这对于识别和隔离当前感染COVID-19的个体至关重要。在此，我们提供了一项概念验证研究，利用Rosetta抗体设计（RAbD）对结合SARS-CoV-2刺突蛋白多种变体的高亲和力抗体进行计算设计。以与SARS-CoV-1（而非SARS-CoV-2）刺突蛋白高亲和力结合的、特征明确的抗体作为模板，并重新设计使其与SARS-CoV-2刺突蛋白高亲和力结合，从而实现了特异性转换。一组设计的抗体经过了实验验证。其中一种设计与包括奥密克戎、德尔塔、武汉和南非刺突蛋白变体在内的多种关注变体结合。
