RESUMEN
The recent emergence and re-emergence of viral infections transmitted by vectors, such as the Zika virus (ZIKV) and Dengue virus (DENV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas of the world. Despite the high morbidity and mortality associated with these viral infections, antiviral therapies are missing. Medicinal plants have been widely used to treat various infectious diseases since millenaries. Several compounds extracted from plants exhibit potent effects against viruses in vitro, calling for further investigations regarding their efficacy as antiviral drugs. Here, we demonstrate that an extract from Psiloxylon mauritianum, an endemic medicinal plant from Reunion Island, inhibits the infection of ZIKV in vitro without exhibiting cytotoxic effects. The extract was active against different ZIKV African and Asian strains, including an epidemic one. Time-of-drug-addition assays revealed that the P. mauritianum extract interfered with the attachment of the viral particles to the host cells. Importantly, the P. mauritianum extract was also able to prevent the infection of human cells by four dengue virus serotypes. Due to its potency and ability to target ZIKV and DENV particles, P. mauritianum may be of value for identifying and characterizing antiviral compounds to fight medically-important flaviviruses.
Asunto(s)
Antivirales/farmacología , Virus del Dengue/efectos de los fármacos , Dengue/tratamiento farmacológico , Magnoliopsida/química , Polifenoles/farmacología , Infección por el Virus Zika/tratamiento farmacológico , Virus Zika/efectos de los fármacos , Animales , Antivirales/química , Células Cultivadas , Chlorocebus aethiops , Dengue/epidemiología , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Plantas Medicinales/química , Polifenoles/química , Reunión/epidemiología , Células Vero , Infección por el Virus Zika/epidemiologíaRESUMEN
The mosquito-borne Zika virus (ZIKV) belongs to the flavivirus genus of the Flaviviridae family. Contemporary epidemic strains of ZIKV are associated with congenital malformations in infants, including microcephaly, as well as Guillain-Barré syndrome in adults. A risk of human-to-human transmission of ZIKV is also well documented. A worldwide research effort has been undertaken to identify safe and effective strategies to prevent or treat ZIKV infection. We show here that extract from Aphloia theiformis, an edible endemic plant from Indian Ocean islands, exerts a potent antiviral effect against ZIKV strains of African and Asian lineages, including epidemic strains. The antiviral effect of A. theiformis extract was extended to clinical isolates of dengue virus (DENV) of the four serotypes in human hepatocytes. A. theiformis inhibited virus entry in host cells by acting directly on viral particles, thus impairing their attachment to the cell surface. Electron microscopic observations revealed that organization of ZIKV particles was severely affected by A. theiformis. We propose a model of antiviral action for A. theiformis against flaviviruses that highlights the potential of medicinal plants as promising sources of naturally-derived antiviral compounds to prevent ZIKV and DENV infections.
Asunto(s)
Extractos Vegetales/farmacología , Plantas Comestibles/química , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Infección por el Virus Zika/tratamiento farmacológico , Virus Zika/efectos de los fármacos , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Ciclo Celular , Proliferación Celular , Células Cultivadas , Chlorocebus aethiops , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Magnoliopsida/química , Reunión/epidemiología , Células Vero , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virologíaRESUMEN
Zika virus (ZIKV) infection is a major public health problem with severe human congenital and neurological anomalies. The screening of anti-ZIKV compounds and neutralizing antibodies needs reliable and rapid virus-based assays. Here, we described a convenient method leading to the rapid production of molecular clones of ZIKV. To generate a molecular clone of ZIKV strain MR766(NIID), the viral genome was directly assembled into Vero cells after introduction of four overlapping synthetic fragments that cover the full-length genomic RNA sequence. Such strategy has allowed the production of a recombinant ZIKV expressing the GFP reporter gene that is stable over two culturing rounds on Vero cells. Our data demonstrate that the ZIKV reporter virus is a very reliable GFP-based tool for analyzing viral growth and measuring the neutralizing antibody as well as rapid screening of antiviral effect of different classes of inhibitors.