具有 ACE2 和抗 Omicron 抗体的 Omicron Spike 三聚体的结构.docxVIP

具有ACE2和抗Omicron抗体的Omicron Spike三聚体的结构 抽象的SARS-CoV-2 Omicron变种已成为主要的感染菌株。我们报告了 Omicron刺突 三聚体本身或与ACE2或抗Omicron抗体复合的结构。大多数Omicron突变 位于刺突蛋白的外表，这会改变许多当前抗体的结合表位。在ACE2结合位 点，补偿性突变增强了 RBD与ACE2的结合。Omicron穗三聚体的RBD和 apo形式都是热力学不稳定的。ACE2-spike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与穗三聚体的结合。一种广谱治疗性抗 体JMB2002已完成1期临床试验，对Omicron保持中和活性。 SARS-CoV-2的Omicron变体是C0VID-19的致病病毒，最初于2021年11 月从南非报道，并迅速成为全球主要毒株（，）。系统发育树分析说明， Omicron独立于先前的关注变体（VOC）进化，包括主要的Alpha、Beta、 Gamma和Delta变体（图1A ） （2-5 ）。与SARS-CoV-2的原始野生型 （WT）毒株相比，Omicron有60个氨基酸突变，其中37个突变位于刺突蛋白 中，这是大多数C0V1D-19疫苗和治疗性抗体的靶标（图1B ））。这种高度 变异反映在不同的行为中，Omicron变体表现出增强的传播、抗体逃避和疫苗 抗性（6 - 8 ）。 Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibodyAbstract The SARS-CoV-2 Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own or in complex with ACE2 or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein, which change binding epitopes to many current antibodies. In the ACE2 binding site, compensating mutations strengthen 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. The Omicron variant of SARS-CoV-2, the causative virus of COVID-19, was initially reported from South Africa in November 2021, and quickly became the dominant strain worldwide (/). Phylogenetic tree analyses reveal that Omicron evolved independently from previous variants of concerns (VOC), including the predominant Alpha, Beta, Gamma, and Delta variants (Fig. 1A) (2- 5)? Compared to the original wildtype (WT) strain of SAR