Suramin hexasodium salt (Synonyms: BAY 205, Germanin, NF 060)

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 < 0.005) and protein (P < 0.005) in both HO-8910 PM and HeLa cells at 48 h ^[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.

References:
[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.