The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC₅₀ in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.

中文翻译：

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siRNA 靶向并抑制广泛的 SARS-CoV-2 感染，包括 Delta 变体

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变体的出现改变了 COVID-19 大流行的轨迹，并增加了疫苗策略长期效率的一些不确定性。开发针对各种 SARS-CoV-2 变体的新疗法势在必行。我们在这里设计了一种可吸入的 siRNA C6G25S，它涵盖了当前 SARS-CoV-2 变体的 99.8%，并且能够在皮摩尔范围内抑制体外IC ₅₀ 的主要菌株，包括 Alpha、Delta、Gamma 和 Epsilon. 此外，C6G25S 可通过预防性治疗完全抑制肺部感染性病毒粒子的产生，并通过联合治疗在 K18-hACE2 转基因小鼠中减少 96.2% 的病毒粒子，同时显着预防病毒相关的广泛肺泡损伤、血管血栓、和免疫细胞浸润。我们的数据表明，C6G25S 为对抗 COVID-19 大流行提供了另一种有效的方法。