The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

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.

Could the Inhibition of Endo-Lysosomal Two-Pore Channels (TPCs) by the Natural Flavonoid Naringenin Represent an Option to Fight SARS-CoV-2 Infection?

“…Interestingly, in the same study (Nahmias et al, 2008), Nar was shown to be effective to reduce Hepatitis C virus secretion by 80% when added at 200 µM in infected Huh7.5.1 human hepatoma cell line. Moreover, that Nar treatment could be a promising strategy to inhibit virus replication and infection is further confirmed by interesting studies on the influenza A virus, dengue virus and Zika virus (Dong et al, 2015;Frabasile et al, 2017;Cataneo et al, 2019). Antiviral effect of some flavonoids and Nar through blocking viral proteases activity in different experimental models has been also reported (de Sousa et al, 2015;Lulu et al, 2016;Lim et al, 2017;Jo et al, 2020).…”

Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity

“…They are key mediators of various biological processes in plants, such as nitrogen fixation, photosynthesis, energy transfer, and anti-oxidation [ 15 ]. Moreover, their activities extended towards anti-cancer, antivirals [ 10 , 12 , 17 ], and anti-inflammation [ 29 , 30 ]. Generally, flavanones are further metabolized to flavones by the addition of a double bond to C2–C3 of ring C, thus decreasing the aqueous solubility ( Supplementary Figure S6 ) [ 31 ].…”

“…To overcome the challenge, a flavanone substrate with higher solubility was considered as a replacement. Moreover, pinocembrin (5,7-dihydroxyflavanone), was previously reported as a potential inhibitor of dengue [ 10 , 11 ] and Zika viruses [ 12 ] with possible targets at viral NS2B-3 protease [ 12 , 13 , 14 ]. Moreover, anti-flaviviral inhibition was also reported in other flavanones, such as pinostrobin, naringenin, hesperitin, and their derivatives.…”

The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

“…It has been reported that naringenin suppressed respiratory overexpression and eosinophilic airway inflammation in asthma and thus, reduced acute neutrophilic airway inflammation by blocking the NF-κB pathway [ 106 ]. Naringenin has been found to impair replication of several viruses in human cells such as dengue, Zika and Chikungunya viruses [ 107 – 109 ] and to guarantee a significant protection against LPS-induced acute lung injuries through its anti-inflammatory, antioxidant, antinitrosative and antiapoptotic effects [ 110 , 111 ]. Due to its strong anti-inflammatory and anti-oxidant effects, narigenin may be utilized against pneumonia companied with the spread of COVID-19.…”