Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX
Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX
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DOI：
10.1111/jam.13038
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发表时间：
2016-03-01
影响因子：
4
通讯作者：
Bozza, M. T.
中科院分区：
文献类型：
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作者：
Assuncao-Miranda, I.;Cruz-Oliveira, C.;Bozza, M. T.
目的探讨血红素，钴-原卟啉IX和锡-原卟啉IX（CoPPIX和SnPPIX），大环结构组成的四吡咯环与中心金属离子，对登革病毒（DENV）和黄热病病毒（YFV）infection.Methods和ResultsHepG 2细胞治疗后，DENV感染减少感染性颗粒，CoPPIX和SnPPIX不影响病毒RNA含量在感染的细胞。病毒载量的减少仅在DENV与卟啉直接接触时发生，表明对病毒颗粒的直接作用。先前DENV和YFV与血红素、CoPPIX和SnPPIX的孵育导致病毒颗粒以剂量依赖性方式灭活。胆绿素是一种非环状卟啉，不能抑制测试的病毒。用卟啉预处理的DENV 2感染HepG 2细胞导致病毒蛋白质合成、RNA复制和细胞死亡减少或消除。结论Heme、CoPPIX和SnPPIX对DENV和YFV有明显的抑制作用，但对DENV和YFV无明显的抑制作用。本研究的意义和影响这些结果为卟啉类化合物的治疗应用提供了可能性，它们作为设计针对DENV和YFV的新的抗病毒药物的模型的用途。
AimsTo investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection.Methods and ResultsTreatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death.ConclusionsHeme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells.Significance and Impact of the StudyThese results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV.