Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA.
Viruses. 2023 Mar 7;15(3):696. doi: 10.3390/v15030696.
Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The quantification of viral production indicated the antiviral activity of TIZ. The protein profiles in infected Vero cells treated and not treated with TIZ were analyzed using the label-free quantitative proteomic approach. TIZ was able to inhibit virus replication mainly intracellularly after DENV-2 penetration and before the complete replication of the viral genome. Additionally, the study of the protein profile of infected not-treated and infected-treated Vero cells showed that TIZ interferes with cellular processes such as intracellular trafficking and vesicle-mediated transport and post-translational modifications when added after infection. Our results also point to the activation of immune response genes that would eventually lead to a decrease of DENV-2 production. TIZ is a promising therapeutic molecule for the treatment of DENV-2 infections.
登革热病毒是巴西一种重要的循环虫媒病毒，在全球范围内可导致高发病率和死亡率，除了影响公共卫生外，还带来了巨大的经济和社会负担。在这项研究中，我们评估了替硝唑（TIZ）在 Vero 细胞培养物中的生物学活性、毒性和抗登革热病毒 2 型（DENV-2）活性。TIZ 在抑制包括细菌、原生动物和病毒在内的不同病原体方面具有广谱作用。用 DENV-2 感染细胞 1 小时，然后用不同浓度的药物处理 24 小时。病毒产量的定量表明了 TIZ 的抗病毒活性。用无标记定量蛋白质组学方法分析了用 TIZ 处理和未处理的感染 Vero 细胞的蛋白质图谱。TIZ 能够在 DENV-2 穿透后和病毒基因组完全复制之前主要在细胞内抑制病毒复制。此外，对未处理和感染后用 TIZ 处理的感染 Vero 细胞的蛋白质图谱的研究表明，TIZ 会干扰细胞内运输和囊泡介导的运输以及翻译后修饰等细胞过程，当在感染后加入时。我们的结果还表明，免疫反应基因被激活，最终导致 DENV-2 产量下降。TIZ 是治疗 DENV-2 感染的一种很有前途的治疗分子。
