AAC00835-24R1 - Intranasal Liposomal Angiotensin-(1-7) Administration Reduces Inflammation and Viral Load in the lungs during SARS-CoV-2 Infection in K18-hACE2 Transgenic Mice

This study aimed to develop a liposomal formulation of the peptide angiotensin-(1-7) (LAng (1-7)) and evaluate its antiviral, anti-inflammatory effects, and impact on survival in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared using the ethanol injection method, with an average diameter of 100 nm and a polydispersity index of 0.1. After intranasal administration every 12 hours for 5 days, LAng (1-7) extended the survival of the animals compared to control groups, and significantly reduced viral load as well as IL-6 and TNF levels in the lungs. Conventional treatment with remdesivir, administered parenterally, also improved survival and reduced viral load, but had no significant effect on IL-6 levels. Therefore, liposomal Ang-(1-7) emerges as a promising approach to enhance treatment and reduce the severity of respiratory infections such as COVID-19.

本研究旨在开发血管紧张素-(1-7)肽（LAng (1-7)）的脂质体制剂，并评估其抗病毒、抗炎作用，以及对感染严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的转基因K18-hACE2小鼠存活率的影响。该脂质体制剂采用乙醇注入法制备，平均粒径为100 nm，多分散指数为0.1。每12小时鼻内给药一次、连续给药5天后，与对照组相比，LAng (1-7)可延长受试动物的存活时间，并显著降低肺部的病毒载量以及白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）水平。采用胃肠外给药的瑞德西韦（remdesivir）常规治疗，同样可改善受试动物的存活率并降低病毒载量，但对IL-6水平无显著影响。综上，脂质体Ang-(1-7)有望成为改善新型冠状病毒肺炎（COVID-19）等呼吸道感染疾病治疗效果、减轻病情严重程度的极具潜力的治疗策略。