Abstract
The Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. The ZIKV infection is usually asymptomatic or is associated with mild clinical manifestations; however, increased numbers of cases of microcephaly and birth defects have been recently reported. To date, neither a vaccine nor an antiviral treatment has become available to control ZIKV replication. Among the natural compounds recognized for their medical properties, flavonoids, which can be found in fruits and vegetables, have been found to possess biological activity against a variety of viruses. Here, we demonstrate that the citrus flavanone naringenin (NAR) prevented ZIKV infection in human A549 cells in a concentration-dependent and ZIKV-lineage independent manner. NAR antiviral activity was also observed when primary human monocyte-derived dendritic cells were infected by ZIKV. NAR displayed its antiviral activity when the cells were treated after infection, suggesting that NAR acts on the viral replication or assembly of viral particles. Moreover, a molecular docking analysis suggests a potential interaction between NAR and the protease domain of the NS2B-NS3 protein of ZIKV which could explain the anti-ZIKV activity of NAR. Finally, the results support the potential of NAR as a suitable candidate molecule for developing anti-ZIKV treatments.
Highlights
The Zika virus (ZIKV) is an arthropod-borne virus from the Flavivirus genus and the Flaviviridae family that was first isolated from a rhesus monkey from the Zika forest of Uganda in 19471
Double-negative A549 cells were used to establish the cytotoxic concentration for 50% of the culture (CC50), which was calculated as 693.6 μM (Fig. 1C)
The cell nuclei count using Operetta high-content imaging show that NAR (125 μM) did not reduce the number of cells compared to untreated A549 cells (Fig. 1D)
Summary
The Zika virus (ZIKV) is an arthropod-borne virus from the Flavivirus genus and the Flaviviridae family that was first isolated from a rhesus monkey from the Zika forest of Uganda in 19471. Flavonoids are polyphenolic compounds that are present in a wide range of Física Biológica, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil. NAR was shown to present a wide range of activities, including anti-inflammatory and analgesic actions[30,31,32]. NAR was recently shown to have anti-dengue virus activity in vitro[18], and the similarities between these flaviviruses prompted us to test NAR against ZIKV infection in vitro. NAR was shown to present in vitro anti-ZIKV activity against four different strains of recent clinical isolates of the Asian lineage and one classical African lineage. The antiviral activity of NAR seems to occur in the late steps of virus life cycle. In silico docking analysis suggests a close interaction between NAR and the protease domain of ZIKV, strengthening the data from in vitro assays
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