Chen Zhe, Feng Leilei, Wang Lei, Zhang Li, Zheng Binyang, Fu Hua, Li Fengdi, Liu Ligai, Lv Qi, Deng Ran, Xu YanLi, Hu Yongfeng, Zheng Jianhua, Qin Chuan, Bao Linlin, Wang Xiangxi, Jin Qi
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Signal Transduct Target Ther. 2025 Jan 13;10(1):14. doi: 10.1038/s41392-024-02114-6.
The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.1, BA.2, BA.3, BA.4, and BA.5 have developed the capacity to evade neutralization induced by previous vaccination or infection. This evasion highlights the urgency in discovering new monoclonal antibodies (mAbs) with neutralizing activity, especially broadly neutralizing antibodies (bnAbs), to combat the virus.In the current study, we introduced a fully human neutralizing mAb, CR9, that targets Omicron variants. We demonstrated the mAb's effectiveness in inhibiting Omicron replication both in vitro and in vivo. Structural analysis using cryo-electron microscopy (cryo-EM) revealed that CR9 binds to an epitope formed by RBD residues, providing a molecular understanding of its neutralization mechanism. Given its potency and specificity, CR9 holds promise as a potential adjunct therapy for treating Omicron infections. Our findings highlight the importance of continuous mAb discovery and characterization in addressing the evolving threat of COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及其变异株，包括阿尔法、贝塔、伽马、德尔塔以及现在的奥密克戎，在全球范围内传播，构成了重大挑战。随着病毒的不断进化，奥密克戎及其亚型BA.1、BA.2、BA.3、BA.4和BA.5已经具备了逃避先前疫苗接种或感染所诱导的中和作用的能力。这种逃避凸显了发现具有中和活性的新型单克隆抗体（mAb），特别是广谱中和抗体（bnAb）以对抗该病毒的紧迫性。在当前的研究中，我们引入了一种靶向奥密克戎变异株的全人源中和单克隆抗体CR9。我们证明了该单克隆抗体在体外和体内抑制奥密克戎复制的有效性。使用冷冻电子显微镜（cryo-EM）进行的结构分析表明，CR9与由受体结合域（RBD）残基形成的表位结合，从而对其中和机制有了分子层面的理解。鉴于其效力和特异性，CR9有望成为治疗奥密克戎感染的潜在辅助疗法。我们的研究结果凸显了持续发现和表征单克隆抗体在应对不断演变的新冠疫情威胁中的重要性。
