Abstract：
BACKGROUND: Drug resistance is an important factor in the fight against influenza A virus (IAV). Natural products offer a rich source of lead compounds for the discovery of novel antiviral drugs. In a previous study, we isolated the sorbicillinoid polyketide HSL-2 from the mycelium of fungus Trichoderma sp. T-4-1. Here, we show that this compound exerts strong antiviral activity against a panel of IAVs.
METHODS: The immunofluorescence and qRT-PCR assays were used to detect the inhibitory effect of HSL-2 toward the replication of influenza virus and IAV-induced expression of the pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.
RESULTS: The results indicated that HSL-2 inhibited influenza virus replication, and it significantly inhibited IAV-induced overexpression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β through modulating the PPAR-γ/NF-κB pathway. Notably, this effect was decreased when cells were transfected with PPAR-γ siRNA or treated with the PPAR-γ inhibitor T0070907. In addition, HSL-2 was able to attenuate lung inflammatory responses and to improve lung lesions in a mouse model of IAV infection.
CONCLUSIONS: In this paper, we identified a microbial secondary metabolite, HSL-2, with anti-influenza virus activity. This report is the first to describe the antiviral activity and mechanism of action of HSL-2, and it provides a new strategy for the development of novel anti-influenza virus drugs from natural sources.
METHODS: The immunofluorescence and qRT-PCR assays were used to detect the inhibitory effect of HSL-2 toward the replication of influenza virus and IAV-induced expression of the pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.
RESULTS: The results indicated that HSL-2 inhibited influenza virus replication, and it significantly inhibited IAV-induced overexpression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β through modulating the PPAR-γ/NF-κB pathway. Notably, this effect was decreased when cells were transfected with PPAR-γ siRNA or treated with the PPAR-γ inhibitor T0070907. In addition, HSL-2 was able to attenuate lung inflammatory responses and to improve lung lesions in a mouse model of IAV infection.
CONCLUSIONS: In this paper, we identified a microbial secondary metabolite, HSL-2, with anti-influenza virus activity. This report is the first to describe the antiviral activity and mechanism of action of HSL-2, and it provides a new strategy for the development of novel anti-influenza virus drugs from natural sources.
摘要：
背景：耐药性是对抗甲型流感病毒（IAV）的重要因素。天然产物为发现新型抗病毒药物提供了丰富的先导化合物来源。在之前的研究中,我们从木霉属真菌的菌丝体中分离出山梨醇类聚酮HSL-2。T-4-1.这里,我们表明该化合物对一组IAV具有很强的抗病毒活性。
方法：采用免疫荧光和qRT-PCR检测HSL-2对流感病毒复制的抑制作用和IAV诱导的促炎细胞因子如TNF-α的表达。IL-6和IL-1β。
结果：结果表明HSL-2抑制流感病毒的复制，显著抑制IAV诱导的促炎细胞因子TNF-α的过表达,IL-6和IL-1β通过调节PPAR-γ/NF-κB途径。值得注意的是,当用PPAR-γsiRNA转染细胞或用PPAR-γ抑制剂T0070907处理细胞时,这种效应降低。此外,在IAV感染的小鼠模型中，HSL-2能够减弱肺部炎症反应并改善肺部病变。
结论：在本文中，我们发现了一种微生物次生代谢产物,HSL-2，具有抗流感病毒活性。该报告首次描述了HSL-2的抗病毒活性和作用机制，为从天然来源开发新型抗流感病毒药物提供了新的策略。
方法：采用免疫荧光和qRT-PCR检测HSL-2对流感病毒复制的抑制作用和IAV诱导的促炎细胞因子如TNF-α的表达。IL-6和IL-1β。
结果：结果表明HSL-2抑制流感病毒的复制，显著抑制IAV诱导的促炎细胞因子TNF-α的过表达,IL-6和IL-1β通过调节PPAR-γ/NF-κB途径。值得注意的是,当用PPAR-γsiRNA转染细胞或用PPAR-γ抑制剂T0070907处理细胞时,这种效应降低。此外,在IAV感染的小鼠模型中，HSL-2能够减弱肺部炎症反应并改善肺部病变。
结论：在本文中，我们发现了一种微生物次生代谢产物,HSL-2，具有抗流感病毒活性。该报告首次描述了HSL-2的抗病毒活性和作用机制，为从天然来源开发新型抗流感病毒药物提供了新的策略。
