James A. Haley Veterans Hospital, Tampa, FL 33612, USA.
Center for Research and Education in Nanobioengineering, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Viruses. 2023 Jun 24;15(7):1429. doi: 10.3390/v15071429.
Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.
新兴的冠状病毒，如 2003 年的 SARS-CoV-1、2012 年的 MERS-CoV 和 2019 年的 SARS-CoV-2（CoV-2），已经导致数百万人死亡。这些病毒与呼吸道合胞病毒（RSV）和流感一起，增加了现有的呼吸道感染负担。目前针对呼吸道病毒的治疗方法有限，广谱治疗仍然是一个未满足的需求。由于纤维的肠道发酵产生具有抗病毒潜力的短链脂肪酸（SCFA），因此研究了基于脂肪酸的广谱抗病毒药物。脂肪酸的分子对接表明，α-亚麻酸（ALA）可能与 CoV-2-S、NL63-CoV-S 和 RSV-F 相互作用，并且含有 ALA 的脂质体直接与 CoV-2 相互作用，降解病毒颗粒。此外，ALA 和 SCFA-醋酸盐的组合协同抑制 CoV2-N 的表达，显著降低 Calu-3 细胞中的病毒斑形成和 IL-6 和 IL-1β 转录表达，同时增加 IFN-β 的表达。在 RSV 感染的 A549 细胞中也观察到类似的效果。此外，用含有 ALA 的脂质体包裹醋酸盐处理感染了鼠适应的 SARS-CoV-2（MA10）的小鼠，显著降低了肺组织中的病毒斑形成单位以及感染相关的肺炎症和细胞因子。综上所述，这些结果表明，含有 ALA 的脂质体包裹醋酸盐可以成为一种有前途的针对呼吸道感染的广谱抗病毒治疗方法。
