Modeling potential drugs for Zika virus in animal and in vitro platforms: what is the current state of the art?

INTRODUCTION: The Zika virus (ZIKV) poses a significant public health threat due to its association with congenital Zika syndrome (CZS) and severe neurological disorders. Since its discovery, ZIKV has transitioned from sporadic outbreaks to a major epidemic in Brazil in 2015, which highlighted the urgent need for effective therapies, especially for vulnerable groups like pregnant women and newborns.

AREAS COVERED: This review provides a comprehensive overview of recent advancements in ZIKV drug discovery and their current stage of development, with a particular focus on those tested in animal models from 2018 to date, excluding vaccine candidates. Repurposed drugs, such as molnupiravir and sofosbuvir, have shown the potential to inhibit viral replication and mitigate disease. Novel compounds targeting viral proteins and host-directed therapies are also discussed. Furthermore, advanced in vitro models, including brain organoids, have offered critical insights into therapeutic efficacy.

EXPERT OPINION: Although some preclinical models have identified potential drugs ready for human translation, no protocol has yet been established for treating ZIKV infection. Currently, the treatment involves supportive care, managing symptoms, and preventing complications, especially for pregnant women. Ongoing research aims to develop specific antiviral therapies and vaccines; however, no such options are currently available.