Developing animal models of Zika virus infection for novel drug discovery

ABSTRACT

Introduction: Just before the Brazilian outbreak, Zika virus was related to a mild infection, causing fever and skin rash. Congenital Zika Syndrome was first described in Brazil, causing microcephaly and malformations in newborns. Three years after the outbreak, the mechanisms of Zika pathogenesis are still not completely elucidated. Moreover, as of today, there is still no approved vaccine that can be administered to the susceptible population. Considering the unmet clinical need, animal models represent an unprecedented opportunity to study Zika pathophysiology and test drugs for the treatment and prevention of vertical transmission.

Areas covered: The authors explore the current knowledge about Zika through animal models and advancements in drug discovery by highlighting drugs with the greatest potential to treat ZIKV infection and block vertical transmission.

Expert opinion: Some drugs used to treat other infections have been repurposed to treat Zika infection, reducing the cost and time for clinical application. One promising example is Sofosbuvir, which protected mice models against Zika pathogenesis by preventing vertical transmission. Importantly, there is a lack on exploration on the long-term effects of Zika Congenital Syndrome, as well as the possible ways to treat its sequelae.

KEYWORDS:

• Animal model
• azithromycin
• chloroquine
• congenital Zika syndrome
• drug discovery
• galidesivir
• niclosamide
• novobiocin
• sofosbuvir
• ZIKV

Article highlights

• Mice models have been very powerful tools to understand ZIKV mechanism of pathogenesis, as well as for drug screening;

• Signs of ZIKV pathogenesis differs depending on the animal model and species, routes of viral administration and viral strain;

• Although drugs against ZIKV have been widely explored in vitro, there are still few drugs tested in vivo;

• The use of monkeys as animal models to test anti-ZIKV drugs is also encouraging;

• Sofosbuvir is a FDA-approved drug that can prevent ZIKV infection in adults and blocks ZIKV vertical transmission.

This box summarizeskey points contained in the article.

Acknowledgments

The authors would like to thank Stephanie Hodeib for her help revising this manuscript.

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 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (18/16748-8; 16/02978-6), the Brazilian NGO ‘the tooth fairy project’ and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior-Brasil (CAPES)-Finance Code 001; and the CNPq.