(L4991) Tamoxifen as a Zika Virus Therapeutic

Scott Grady (Saint Louis University)| Amelia Pinto (Saint Louis University)| Mariah Hassert (Saint Louis University)| James Brien (Saint Louis University)| Christopher Arnatt (Saint Louis University)

Zika virus (ZIKV) is an arbovirus belonging to the flaviviridae family with a risk assessment that has increased in recent years and was labeled a global health emergency by the WHO in 2016. There are currently no FDA approved treatment options available for ZIKV, so expeditious development of treatment options is urgent. An on-market drug, tamoxifen (Tam), was selected as a promising candidate for repurposing due to its wide range of biological activities and because it has already been shown to possess activity against hepatitus C (HCV), a related flavivirus. Anti-ZIKV activity of Tam was assessed by compound screens using infectious virus and mechanistic details were gleaned from time of addition and virucidal studies. Tam and the active form, 4-hydroxytamoxifen, showed promising antiviral activity in initial compound screening and up to 8 hours post infection, though the virucidal assay indicated that they do not possess any direct virucidal activity. Additionally, Tam was assessed for its activity against ZIKV in the human male germ cell line, SEM-1, and virus titers show diminished replication of ZIKV over a seven day period compared to controls. These data indicate that Tam has potential to be repurposed as an anti-ZIKV therapeutic and warrants further investigation.