An update on preclinical pregnancy models of Zika virus infection for drug and vaccine discovery

ABSTRACT

Introduction

Congenital Zika syndrome is caused by Zika virus (ZIKV) infection during pregnancy and can culminate in structural and neurological defects in the fetus, including a spectrum of symptoms such as brain calcifications, hydrocephalus, holoprosencephaly, lissencephaly, ventriculomegaly, and microcephaly. Using animal models to study ZIKV infection during pregnancy represents a critical tool for understanding ZIKV pathophysiology, drug testing, vaccine development, and prevention of vertical transmission.

Areas covered

In this review, the authors cover state-of-the-art preclinical pregnancy models of ZIKV infection for drug discovery and vaccine development to prevent vertical transmission.

Expert opinion

The discovery of drugs against ZIKV infection represents an urgent necessity, and until now, no effective drug that can prevent the effects of vertical transmission has been tested in humans. Even after six years of the ZIKV outbreak in Brazil, no drugs or vaccines have been approved for use in humans. In part, this failure could be related to the lack of translatability from available preclinical models to humans.

KEYWORDS:

• ZIKV
• congenital Zika syndrome
• animal model
• pregnancy models
• drug discovery
• vaccine

Article highlight

• At present, there are no approved drug treatments or vaccines for ZIKV infection.

• Animal models are an essential tool for understanding ZIKV pathogenesis and vertical transmission. Animal models are also important tools for drug screening and discovery and vaccine development.

• Several candidate vaccines have been under investigation for ZIKV infection, some of which are still in the early developmental stages, including the preclinical model stage, while others are in clinical development.

• Sofosbuvir seems to be a promising therapeutic option since it is FDA-approved, blocks ZIKV replication, and is a drug designed to target flaviviruses.

• One concern regarding current preclinical models of ZIKV infection is their lack of translatability to human subjects. Nevertheless, they represent a crucial tool in the fight against ZIKV infection.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was sponsored by The São Paulo Research Foundation - FAPESP (via grants 16/02978-6 and 2018/16748-8), the Brazilian NGO ‘the tooth fairy project’ and by the National Council for Scientific and Technological Development -CNPq via grant 169784/2017-7.