The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai 201203, China.
Science. 2022 Mar 4;375(6584):1048-1053. doi: 10.1126/science.abn8863. Epub 2022 Feb 8.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的奥密克戎变体已成为主要的感染株。我们报告了奥密克戎刺突三聚体自身以及与血管紧张素转化酶 2（ACE2）或抗奥密克戎抗体复合物的结构。大多数奥密克戎突变位于刺突蛋白表面，并改变了与许多现有抗体的结合表位。在 ACE2 结合位点，补偿性突变增强了受体结合域（RBD）与 ACE2 的结合。RBD 和奥密克戎刺突三聚体的apo 形式在热力学上都是不稳定的。ACE2-刺突复合物中不寻常的 RBD-RBD 相互作用支持开放构象，并进一步加强 ACE2 与刺突三聚体的结合。一种已完成 1 期临床试验的广谱治疗性抗体 JMB2002 保持对奥密克戎的中和活性。JMB2002 与 RBD 的结合不同于其他已鉴定的抗体，并抑制 ACE2 的结合。
