Abstract Highly active antiretroviral therapy (HAART) has been successful in reducing human immunodeficiency virus (HIV)-1-associated morbidity and mortality since its introduction in 1996. However, it fails to eradicate HIV-1 infection. The high cost of life-long highly active antiretroviral therapy and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is a complementary and alternative medicine, and serves as a rich resource for new drug development. Despite the almost 100 plant-derived compounds that are in clinical trials, few target HIV-1 infection. In this study, we discovered that Sanguisorba officinalis extract (SOE) has anti-HIV-1 properties. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2), with respective IC50 values of 1.91 ± 0.16 μg/mL and 3.70 ± 0.53 μg/mL. SOE also inhibited simian immunodeficiency virus infection but failed to block vesicular stomatitis virus, severe acute respiratory syndrome coronavirus, and influenza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effect on postentry events of HIV-1 replication. Because SOE pretreatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity, we can state that SOE probably blocks entry by acting on the viral envelope directly. In addition, SOE was able to inhibit reverse transcriptase inhibitor resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease inhibitor resistant strain (PI-2840). Our findings demonstrate SOE as a novel and specific entry inhibitor, which sheds light on the discovery of anti-HIV-1 drugs from traditional herbal medicines.

中文翻译：

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药材桑树提取物抑制人体免疫缺陷病毒1的进入

摘要 高效抗逆转录病毒疗法 (HAART) 自 1996 年推出以来已成功降低了人类免疫缺陷病毒 (HIV)-1 相关的发病率和死亡率。然而，它未能根除 HIV-1 感染。终生高效抗逆转录病毒治疗的高昂费用以及 HIV-1 感染者耐药性的出现，给新的抗病毒药物和替代药物的发现带来了新的压力。中药（TCM）是一种补充和替代药物，是新药开发的丰富资源。尽管有近 100 种植物衍生化合物处于临床试验阶段，但很少有针对 HIV-1 感染的。在这项研究中，我们发现桑吉索提取物 (SOE) 具有抗 HIV-1 特性。使用基于细胞的测定和单周期荧光素酶报告病毒假型与来自 HIV-1 或对照病毒的包膜，我们发现 SOE 对 CCR5 和 CXCR4 嗜性 HIV-1（ADA 和 HXB2）表现出显着的抑制能力，各自的 IC50 1.91 ± 0.16 μg/mL 和 3.70 ± 0.53 μg/mL 的值。SOE 也能抑制猿猴免疫缺陷病毒感染，但未能阻断水泡性口炎病毒、严重急性呼吸综合征冠状病毒和流感 H5N1 假病毒。此外，我们表明 SOE 对 HIV-1 复制的进入后事件没有影响。因为用病毒而不是用表达病毒受体的细胞系预处理 SOE 显示出最大的抑制活性，我们可以说 SOE 可能通过直接作用于病毒包膜来阻止进入。此外，SOE 能够抑制逆转录酶抑制剂抗性病毒（K103N、Y188L 和 K103N/Y188L/G190A）和蛋白酶抑制剂抗性菌株 (PI-2840)。我们的研究结果表明 SOE 是一种新型的特异性进入抑制剂，这为从传统草药中发现抗 HIV-1 药物提供了线索。