**5. Prevention and control of ZIKV infection: Potential candidates in pregnant women**

In general, pregnancy is a challenge for prevention and control infectious diseases regard to a safe drug or vaccine development to do not disturb the innate/adaptive

*Innate Immunity Modulation during Zika Virus Infection on Pregnancy: What We Still Need… DOI: http://dx.doi.org/10.5772/intechopen.94861*

immunity homeostasis, however, there were no drugs approved for ZIKV infection treatment [28–30]. Here, drugs and vaccines candidates tested in animal models or in newborns will be described with details (**Table 1**).

#### **5.1 Type III interferon: Potential efficacy and safety for immunotherapy**

Type III interferon has been emerging as an efficient and low damaging therapeutic agent not only directed for the virus but also for fungal and bacterial infections, as well as cancer, autoimmune, and vascular diseases [54]. The more restricted expression of IFNLR1 likely contributes to the improved safety profile of IFN-λl in clinical studies compared to type I IFN. Pegylated IFN-λ1 have already been tested in phase 2b clinical trial to chronic hepatitis C treatment and hepatitis B, associated with improved rates of virologic response with fewer extrahepatic adverse events compared to pegylated IFN-α [125]. Even though it was deemed less effective than alternative treatments for these infections, pegylated- IFN- λ can be potential candidate ready for deployment if new indications are identified [126]. There are other viral targets for IFN- λ therapy been tested in murine models: norovirus [127], and influenza virus [128], and west nile virus – last one is another member of Flaviviridae family. It is noteworthy the effect of IFN-λ on infection with west nile virus, an encephalitic flavivirus: Treatment of IFNLR1 knockout mice with pegylated IFN-λ2 resulted in decreased blood–brain barrier permeability, reducing west nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge [129].

The effectiveness and low damage treatments for other correlated viral infections, combined with the protagonist of IFN-λs as immunoregulatory and antiviral agent in ZIKV raise the idea of IFN-λs as ZIKV therapy, and some groups already achieve exciting good results. Concerning ZIKV infections, Jagger, et al., (2017) suggest that IFN-λ2 treatment could be a safe solution to minimize Congenital Zika Syndrome severe outcomes. Using a type III interferon-deficient mouse model, authors showed that these animals had an increase of ZIKV replication in the placenta under ZIKV infection, and treatment of pregnant mice with IFN-λ2 reduced ZIKV viremia [26]. Considering the vaginal epithelium as the first line of defense against sexually transmitted ZIKV, treatment of primary human vaginal and cervical epithelial cells lineages with IFN-λ induces host defense transcriptional signatures with augmented expression of ISGs (IFI44L, OASL, OAS1, and MX1) and inhibition of ZIKV replication. Female mice submitted to treatment with IFN-λ and intravaginal ZIKV transmission showed low levels of virus replication in the female reproductive tract with a hormonal stage-dependent role [130].

## **5.2 Direct-acting antiviral therapy based on RNA-dependent RNA polymerase inhibitors**

Some studies were driving to evaluate effects of independent direct-acting antiviral drugs on Zika virus infection (**Table 1**), as sofosbuvir, an FDA-approved nucleotide analog inhibitor of the hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) [131, 132]. In vitro and *in vivo* studies have been demonstrated effectiveness of sofosbuvir as antiviral drugs to treat Zika and Dengue virus infection [133–135]. Mesci et al., 2018 reported that sofosbuvir was promisor to block vertical transmission of Zika virus in pregnancy using mice models [136]. Again, sofosbuvir shows to play a role in virus replication inhibition. Another flaviviral inhibitor NITD008, an adenosine analog inhibiting the RNA-dependent RNA polymerase activity through chain-termination [137], has been shown to reduce the

