COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. Accordingly, wild type (wt), but not mutated (m), AIDS peptide inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 in human lungs cells. Interestingly, intranasal intoxication of C57/BL6 mice with recombinant SARS-CoV-2 spike S1 led to fever, increase in IL-6 in lungs, infiltration of neutrophils into the lungs, arrhythmias, and impairment in locomotor activities, mimicking some of the important symptoms of COVID-19. However, intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19.

Graphical Abstract

中文翻译：

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SARS-CoV-2 (AIDS) 肽的 ACE-2 相互作用域抑制炎症以减少发烧并保护小鼠的肺和心脏：对 COVID-19 治疗的意义

COVID-19 是由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病毒株引起的传染性呼吸道疾病，到目前为止，还没有针对 COVID-19 的有效疗法。由于 SARS-CoV-2 与血管紧张素转换酶 2 (ACE2) 结合进入宿主细胞，为了从治疗角度靶向 COVID-19，我们设计了一种与 SARS-CoV-2 (AIDS) 的 ACE2 相互作用域相对应的六肽) 抑制含有受体结合域的尖峰 S1 和 ACE-2 之间的关联。因此，野生型 (wt) 但未突变 (m) 的 AIDS 肽抑制 SARS-CoV-2 刺突 S1 诱导的 NF-κB 活化和人肺细胞中 IL-6 的表达。有趣的是，用重组 SARS-CoV-2 刺突 S1 对 C57/BL6 小鼠进行鼻内中毒会导致发烧，肺部 IL-6 增加，中性粒细胞浸润到肺部、心律失常和运动活动受损，与 COVID-19 的一些重要症状相似。然而，在 SARS-CoV-2 刺突 S1 中毒的小鼠中，用 wtAIDS 而不是 mAIDS 进行鼻内治疗，肽可以减少发烧、保护肺部、改善心脏功能并增强运动活动。因此，wtAIDS 选择性靶向 ACE2 与 SARS-CoV-2 的相互作用可能对 COVID-19 有益。

图形概要