Suramin hexasodium salt is a polysulfonated naphthylurea with various biological activities. Suramin hexasodium salt is a DNA topoisomerase II inhibitor with an IC50 of 5 μM [1].
Suramin hexasodium salt at 300–600 μg/ml significantly inhibited HO-8910 PM and HeLa cell growth at 24 h, in both a time-dependent and dose-dependent manner, with an IC50 of 320 μg/ml and 475 μg/ml, respectively. Suramin hexasodium salt at 300 μg/ml significantly decreased the expression of Hpa mRNA (P?[2]. Suramin hexasodium salt shows antiviral activity against the newly emerged virus strain SARS-CoV-2 [3,4].Solution based assays of RdRp inhibition determined that the half-maximal inhibition concentration (IC50) of suramin hexasodium salt is 0.26?μM, Cell-based experiments indicated that suramin hexasodium salt was able to inhibit SARS-CoV-2 duplication in Vero E6 cells with a half-maximal effective concentration (EC50) of roughly 2.9?μM [3].Suramin hexasodium salt treatment of infected Vero E6 cells led to a reduction in extracellular viral RNA levels of up to 3 log. The highest concentration of compound that was used proved harmless to the cells; also, cytotoxicity was observed previously only above 5?mM. Suramin hexasodium salt also displayed antiviral efficacy in a human lung epithelial cell line, and we observed a >2 log reduction in levels of infectious virus progeny in suramin hexasodium salt -treated cells (CC50/EC90?=?>55) [4].
Suramin hexasodium salt has therapeutic effects on CHIKV-infected mice. Suramin hexasodium salt treatment ameliorated foot swelling and reduced inflammatory infiltration, which corresponded to reduced viremia and viral antigen expression in infected tissues. Suramin hexasodium salt induces a dose-dependent reduction in foot swelling in CHIKV 0810bTw-infected mice, and the vary degrees of decreased viremia that was detected in suramin hexasodium salt -treated mice further confirmed therapeutic effects of this drug. In the time-related assay, a single dose of 2 mg suramin hexasodium salt (at 4 h pre-infection) or double doses of 2 mg suramin hexasodium salt (at 1 dpi and 3 dpi) significantly decreased disease score and viremia compared to mock-treated mice.
参考文献:
[1]. Bojanowski K, et al. Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcomacells. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3025-9.
[2]. Li, H.; Li, H.; Qu, H.; et al. Suramin inhibits cell proliferation in ovarian and cervical cancer by downregulating heparanase expression. Cancer Cell Int. 2015, 15, 1–11
[3]. Yin, W. et al. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin. Nat. Struct. Mol. Biol. 28, 319–325 (2021).
[4]. Salgado-Benvindo, C., Thaler, M., Tas, A., Ogando, N. S., et al. Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle. 2020. Antimicrob. Agents Chemother. 20, DOI: 10.1128/AAC.00900-20
[5]. Kuo SC, Wang YM, Ho YJ, Chang TY, Lai ZZ, Tsui PY, Wu TY, Lin CC. 2016. Suramin treatment reduces chikungunya pathogenesis in mice. Antiviral Res 134:89–96.
苏拉明六钠盐是一种具有多种生物活性的多磺化萘脲。 Suramin hexasodium salt 是一种 DNA 拓扑异构酶 II 抑制剂，IC50 为 5 μM [1]。
300-600 μg/ml 的苏拉明六钠盐在 24 小时内以时间依赖性和剂量依赖性方式显着抑制 HO-8910 PM 和 HeLa 细胞的生长，IC50分别为 320 μg/ml 和 475 μg/ml。 300 μg/ml 苏拉明六钠盐显着降低 HO-8910 PM 和 HeLa 细胞在 48 h 时 Hpa mRNA (P><>0.005) 和蛋白质 (P><>0.005) 的表达[2]。苏拉明六钠盐对新出现的病毒株 SARS-CoV-2 [3,4] 显示出抗病毒活性。基于溶液的 RdRp 抑制测定确定了半数最大抑制浓度 (IC50 ) 的苏拉明六钠盐为 0.26 μM，基于细胞的实验表明，苏拉明六钠盐能够以半数最大有效浓度 (EC50< /sub>) 大约为 2.9μM [3]。苏拉明六钠盐处理受感染的 Vero E6 细胞导致细胞外病毒 RNA 水平降低高达 3 log。使用的最高浓度的化合物被证明对细胞无害；此外，以前仅在 5mM 以上观察到细胞毒性。苏拉明六钠盐在人肺上皮细胞系中也显示出抗病毒功效，我们观察到苏拉明六钠盐处理的细胞中感染性病毒后代水平的 >2 log 降低 (CC50/EC90 = >55) [ 4].
苏拉明六钠盐对感染 CHIKV 的小鼠具有治疗作用。苏拉明六钠盐治疗改善了足部肿胀并减少了炎症浸润，这对应于受感染组织中病毒血症和病毒抗原表达的减少。苏拉明六钠盐诱导 CHIKV 0810bTw 感染小鼠足部肿胀的剂量依赖性减少，并且在苏拉明六钠盐处理的小鼠中检测到的不同程度的病毒血症减少进一步证实了该药物的治疗效果。在与时间相关的测定中，单剂量 2 mg 苏拉明六钠盐（在感染前 4 小时）或双剂量 2 mg 苏拉明六钠盐（在 1 dpi 和 3 dpi）与模拟相比显着降低疾病评分和病毒血症-治疗小鼠。
| Cell experiment [1]: | |
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Cell lines |
Vero E6 and Calu-3 |
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Preparation Method |
Vero E6 and Calu-3 cells were preincubated for 30?min with 2-fold serial dilutions of a starting concentration of 200 μM Suramin hexasodium salt and subsequently infected with 2?×?104 PFU of SARS-CoV-2 (MOI of 1 on Vero E6 cells) in 50?μl medium with compound. |
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Reaction Conditions |
200μM for 16 hours or 21 hours |
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Applications |
RT-qPCR revealed that the SARS-CoV-2 RNA levels decreased upon Suramin hexasodium salt treatment in a dose-dependent manner, showing a 3-log reduction at the highest concentration tested (200?μM) |
| Animal experiment [2]: | |
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Animal models |
C57BL/6JNarl (B6) mice |
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Preparation Method |
Suramin hexasodium salt was diluted in normal saline, and indicated doses were administered at 4 h pre-infection, 1day post-infection or/and 3day post-infection (dpi) via the intraperitoneal (ip) route. Specifically, each dose comprised 0, 0.25, 0.5, 1 or 2 mg suramin hexasodium salt. |
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Dosage form |
Intraperitoneal injection, 0, 0.25, 0.5, 1 or 2 mg |
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Applications |
Viral loads in sera of mock-treated mice infected with the 0810bTw, 0611aTw and 0706aTw CHIKV strains at the 2 dpi peak were 5.8, 3 and 4.2 Log10 CCID50/ml, respectively (Fig. 2A). To parallel, viral titers of suramin hexasodium salt-treated sera after received two doses (pre 4 h and 1 dpi) were 5, 2.5 and 3.8 Log10 CCID50/ml for 0810bTw, 0611aTw and 0706aTw strains, respectively. |
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参考文献: [1]. Salgado-Benvindo, C., Thaler, M., Tas, A., Ogando, N. S., et al. Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle. 2020. Antimicrob. Agents Chemother. 20, DOI: 10.1128/AAC.00900-20. [2]. Kuo SC, Wang YM, Ho YJ, Chang TY, Lai ZZ, Tsui PY, Wu TY, Lin CC. 2016. Suramin treatment reduces chikungunya pathogenesis in mice. Antiviral Res 134:89–96. |
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