Alfasigma SpA, Biotechnology R&D, Via Pontina Km 30.400, Pomezia, 00071 Rome, Italy.
ASST Papa Giovanni XXIII, Piazza OMS, 1, 24127 Bergamo, Italy.
Mol Ther. 2022 May 4;30(5):1979-1993. doi: 10.1016/j.ymthe.2022.02.013. Epub 2022 Feb 12.
As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single-chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the Delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Because of their high efficiency, remarkable stability, resilience to nebulization, and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.
截至 2021 年 12 月，由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）仍然是全球紧急情况，急需新型治疗方法。在这里，我们描述了人类单链可变片段（scFv）抗体（76clAbs），该抗体可阻断 SARS-CoV-2 刺突蛋白上对 ACE2 介导进入细胞至关重要的表位。76clAbs 中和了 Delta 变体和其他正在监测的变体（VBMs），并抑制了刺突介导的肺细胞-细胞融合，这是 COVID-19 病理学的一个关键特征。在两个独立的动物模型中，鼻内给药可对抗感染。由于其高效、显著的稳定性、对雾化的弹性以及生产成本低，76clAbs 可能成为 SARS-CoV-2 感染患者快速、可自我管理的早期干预的相关工具，而与他们的免疫状态无关。
