PDF(Pubmed)
Abstract：
Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 μg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 μg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2.
摘要：
获得对抗病毒药物的抗性是抗微生物治疗中的重要问题。为了鉴定新的抗病毒化合物，研究了匈牙利南部地区8种植物对单纯疱疹病毒2（HSV-2）的抗病毒活性。测试了植物提取物和植物化合物鼠尾草酸对Vero和HeLa细胞上HSV-2的细胞外和细胞内形式的有效性。通过直接定量PCR(qPCR)测量HSV-2复制。在测试的植物提取物中，丹参迷迭香（S.迷迭香）在0.47μg/mL浓度下显示HSV-2复制减少90.46％。鼠尾草酸,迷迭香中发现的一种主要抗菌化合物，还证明了对HSV-2的细胞外和细胞内形式的显著剂量依赖性抑制。鼠尾草酸的90%抑制浓度(IC90)为25-6.25μg/mL。蛋白质组学和高分辨率呼吸测定表明，鼠尾草酸抑制关键的ATP合成途径，如糖酵解，柠檬酸盐循环，和氧化磷酸化。氧化磷酸化的抑制也抑制HSV-2复制高达39.94倍。这些结果表明鼠尾草酸的抗病毒作用包括通过抑制关键能量产生途径来抑制ATP产生。鼠尾草酸有望成为针对HSV-2的潜在新型抗病毒剂。
