Scientific Publications by FDA Staff

Int J Antimicrob Agents 2019 Jul;54(1):80-4

Phloretin Inhibits Zika Virus Infection by Interfering with the Cellular Glucose Utilization.

Lin SC, Chen MC, Liu S, Callahan VM, Bracci NR, Woodson CM, Dahal B, de la Fuente CL, Lin CC, Wang TT, Kehn-Hall K

Zika virus (ZIKV) is a re-emerging Flavivirus and has been linked to microcephaly and other neurological pathologies. Here, we applied phloretin, a glucose transporter inhibitor naturally derived from plants, to investigate the glucose dependence of ZIKV replication in host cells. In our study, we show that phloretin significantly decreased infectious titers of two ZIKV strains, MR766 (African genotype) and PRVABC59 (Puerto Rico genotype). The 50% Effective Concentration (EC50) of phloretin against MR766 and PRVABC59 are 22.9 and 9.3 µM, respectively. Further analyses demonstrated that decreased viral production was due to host-targeted inhibitions including decreased apoptotic caspase-3 and -7 activities and reduced phosphorylation of AKT/mTOR pathways. Additionally, upon disruption of cellular glucose availability within host cells through use of 2-deoxy-D-glucose, ZIKV propagation was inhibited. Collectively, we demonstrate phloretin inhibition of ZIKV propagation and provide evidence of glucose utilization pathways as being important for ZIKV propagation. The activity of phloretin and its role in inhibiting glucose uptake could provide a useful foundation for the development of ZIKV antivirals.