Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy.
Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2120976119. doi: 10.1073/pnas.2120976119. Epub 2022 May 12.
As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.
随着 2019 年冠状病毒病（COVID-19）大流行的持续，我们非常需要具有高效力、能抵抗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变异株的单克隆抗体（mAb）。在这里，我们使用基于细胞的测定法评估了先前描述的 mAb J08 针对这些变异株的效力，并使用冷冻电镜（cryo-EM）和 X 射线晶体学深入研究了结合相互作用的分子细节。我们表明，mAb J08 对大多数变异株具有低纳摩尔亲和力，并结合在受体结合域（RBD）脊的高处，远离许多变异株突变。这些发现进一步验证了正在进行的使用 mAb J08 作为单克隆疗法的 II/III 期人体临床试验。
