Laboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Trends Pharmacol Sci. 2022 Oct;43(10):838-851. doi: 10.1016/j.tips.2022.06.011. Epub 2022 Jul 25.
Decoy receptor proteins that trick viruses to bind to them should be resistant to viral escape because viruses that require entry receptors cannot help but bind decoy receptors. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for coronavirus cell entry. Recombinant soluble ACE2 was previously developed as a biologic against acute respiratory distress syndrome (ARDS) and verified to be safe in clinical studies. The emergence of COVID-19 reignited interest in soluble ACE2 as a potential broad-spectrum decoy receptor against coronaviruses. In this review, we summarize recent developments in preclinical studies using various high-affinity mutagenesis and Fc fusion approaches to achieve therapeutic efficacy of recombinant ACE2 decoy receptor against coronaviruses. We also highlight the relevance of stimulating effector immune cells through Fc-receptor engagement and the potential of using liquid aerosol delivery of ACE2 decoy receptors for defense against ACE2-utilizing coronaviruses.
诱饵受体蛋白可以欺骗病毒与其结合，因此应该能够抵抗病毒的逃逸，因为需要进入受体的病毒必然会与诱饵受体结合。血管紧张素转化酶 2（ACE2）是冠状病毒进入细胞的主要受体。以前已经开发出重组可溶性 ACE2 作为治疗急性呼吸窘迫综合征（ARDS）的生物制剂，并在临床研究中被证实是安全的。COVID-19 的出现再次引发了人们对可溶性 ACE2 作为一种针对冠状病毒的潜在广谱诱饵受体的兴趣。在这篇综述中，我们总结了使用各种高亲和力突变和 Fc 融合方法的临床前研究的最新进展，这些方法旨在实现重组 ACE2 诱饵受体对冠状病毒的治疗效果。我们还强调了通过 Fc 受体结合刺激效应免疫细胞的相关性，以及使用 ACE2 诱饵受体的液体气溶胶递送用于防御利用 ACE2 的冠状病毒的潜力。
