IGM Biosciences, Mountain View, CA 94043, USA.
Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Viruses. 2024 Apr 28;16(5):697. doi: 10.3390/v16050697.
Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike mutation that lead to immune evasion against monoclonal antibody (mAb) therapy and vaccination, and suggest alternative durable options such as the ACE2-based experimental therapies superior to mAbs to address this unprecedented evolution of Omicron virus. In addition, this type of unique ACE2-based virus-trapping molecules can counter all zoonotic SARS coronaviruses, either from unknown animal hosts or from established wild-life reservoirs of SARS-CoV-2, and even seasonal alpha coronavirus NL63 that depends on human ACE2 for infection.
自 SARS-CoV-2 奥密克戎病毒在全球占据主导地位以来，其持续的不可预测的突变和模式的进化，已经使所有获得授权的免疫治疗药物失效。为了提供充分的免疫保护，病毒的快速进化也需要进行几轮疫苗更新。了解奥密克戎如何进化成不同的亚变种并导致免疫逃逸仍然至关重要，因为这有助于重新评估目前主要在临床实施的干预策略，这些策略作为应对大流行的紧急措施，重要的是，开发新的解决方案。在这里，我们提供了一篇综述，重点关注奥密克戎病毒进化的主要事件，包括导致针对单克隆抗体（mAb）治疗和疫苗接种的免疫逃逸的刺突突变特征，并提出了替代的持久选择，如基于 ACE2 的实验疗法，优于 mAb，以应对奥密克戎病毒的这种前所未有的进化。此外，这种独特的基于 ACE2 的病毒捕获分子可以对抗所有来自未知动物宿主或 SARS-CoV-2 既定野生动物库的人畜共患 SARS 冠状病毒，甚至是依赖人类 ACE2 感染的季节性α冠状病毒 NL63。
