The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.

中文翻译：

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临床级 ACE2 作为阻断 SARS-CoV-2 变异体的通用药物


最近出现的多种 SARS-CoV-2 变种引起了相当大的关注，因为疫苗功效降低并且逃避了中和抗体治疗。因此，制定抑制所有已知和未来 SARS-CoV-2 变体的治疗策略至关重要。在此，我们报告分析的所有 SARS-CoV-2 变体，包括关注变体 (VOC) Alpha、Beta、Gamma、Delta 和 Omicron，均表现出与临床级和 2 期测试的重组人可溶性 ACE2 (APN01) 的结合亲和力增强。重要的是，与参考 SARS-CoV-2 分离株相比，可溶性 ACE2 中和了所有当前 VOC 菌株对 VeroE6 细胞和人肺上皮细胞的感染，其效力显着增强。两个独立实验室验证并证实了对 SARS-CoV-2 变体感染的有效抑制。这些数据表明，世界各地出现的 SARS-CoV-2 变体，包括当前的 VOC 和几种感兴趣的变体，可以被可溶性 ACE2 抑制，为泛 SARS-CoV-2 治疗提供了原理证明。