Instituto de Microbiologia Paulo de Goes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Sci Rep. 2018 Jun 28;8(1):9805. doi: 10.1038/s41598-018-27855-7.
The global situation of diseases transmitted by arthropod-borne viruses such as Dengue (DENV), Yellow Fever (YFV), Chikungunya (CHIKV) and Zika (ZIKV) viruses is alarming and treatment of human infection by these arboviruses faces several challenges. The discovery of broad-spectrum antiviral molecules, able to inactivate different groups of viruses, is an interesting approach. The viral envelope is a common structure among arboviruses, being a potential target for antivirals. Porphyrins are amphipathic molecules able to interact with membranes and absorb light, being widely used in photodynamic therapy. Previously, we showed that heme, Co-protoporphyrin IX (CoPPIX) and Sn-protoporphyrin IX (SnPPIX) directly inactivate DENV and YFV infectious particles. Here we demonstrate that the antiviral activity of these porphyrins can be broadened to CHIKV, ZIKV, Mayaro virus, Sindbis virus and Vesicular Stomatitis virus. Porphyrin treatment causes viral envelope protein loss, affecting viral morphology, adsorption and entry into target cells. Also, light-stimulation enhanced the SnPPIX activity against all tested arboviruses. In summary, CoPPIX and SnPPIX were shown to be efficient broad-spectrum compounds to inactivate medically and veterinary important viruses.
虫媒病毒(如登革热病毒、黄热病病毒、基孔肯雅热病毒和寨卡病毒)引起的疾病在全球范围内令人担忧,治疗这些虫媒病毒感染面临着诸多挑战。广谱抗病毒分子的发现,能够使不同病毒失活,这是一种很有前途的方法。病毒包膜是虫媒病毒的共同结构,是抗病毒药物的潜在靶点。卟啉是一种两亲性分子,能够与膜相互作用并吸收光,广泛应用于光动力疗法。之前,我们已经证明血红素、钴原卟啉 IX(CoPPIX)和锡原卟啉 IX(SnPPIX)可以直接使登革热病毒和黄热病病毒的感染性颗粒失活。在这里,我们证明了这些卟啉的抗病毒活性可以扩展到基孔肯雅热病毒、寨卡病毒、马亚罗病毒、辛德毕斯病毒和水疱性口炎病毒。卟啉处理会导致病毒包膜蛋白丢失,影响病毒形态、吸附和进入靶细胞。此外,光照刺激增强了 SnPPIX 对所有测试的虫媒病毒的活性。综上所述,CoPPIX 和 SnPPIX 是有效的广谱化合物,可以使具有医学和兽医重要性的病毒失活。