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迷迭香酸通过抑制细胞 ATP 合成抑制单纯疱疹病毒复制。

Carnosic Acid Inhibits Herpes Simplex Virus Replication by Suppressing Cellular ATP Synthesis.

机构信息

Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, 6725 Szeged, Hungary.

Réthy Pál County Hospital, Gyulai Str. 18, 5600 Bekescsaba, Hungary.

出版信息

Int J Mol Sci. 2024 May 3;25(9):4983. doi: 10.3390/ijms25094983.

DOI:10.3390/ijms25094983
PMID:38732202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11084413/
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, () 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 (IC) 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

获得抗病毒药物的耐药性是抗菌治疗中的一个重大问题。为了鉴定新的抗病毒化合物,研究了匈牙利南部地区的八种本土植物对单纯疱疹病毒-2(HSV-2)的抗病毒活性。在 Vero 和 HeLa 细胞上,测试了植物提取物和植物化合物迷迭香酸对 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 的复制。在所测试的植物提取物中,()在 0.47μg/mL 浓度下,HSV-2 复制减少了 90.46%。迷迭香中的主要抗菌化合物迷迭香酸也表现出对 HSV-2 的细胞外和细胞内形式的显著剂量依赖性抑制作用。迷迭香酸的 90%抑制浓度(IC)在 25 至 6.25μg/mL 之间。蛋白质组学和高分辨率呼吸测量表明,迷迭香酸抑制了关键的 ATP 合成途径,如糖酵解、柠檬酸循环和氧化磷酸化。氧化磷酸化的抑制也将 HSV-2 的复制抑制了高达 39.94 倍。这些结果表明,迷迭香酸的抗病毒作用包括通过抑制关键的能量产生途径来抑制 ATP 的产生。迷迭香酸有望成为一种针对 HSV-2 的新型潜在抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/bf69343f7773/ijms-25-04983-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/bf69343f7773/ijms-25-04983-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/b6b775ce114c/ijms-25-04983-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/f17fc3e27592/ijms-25-04983-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/6505dcc1f512/ijms-25-04983-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/86d826b8c0cd/ijms-25-04983-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6816/11084413/bf69343f7773/ijms-25-04983-g007.jpg

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