Zika Fever: Development of Diagnostics, Prevention and Treatment

Abstract

This review is devoted to the analysis of the literature data on the development of tools for diagnostics of Zika fever and detection of etiological agent – Zika virus (ZIKV) belonging to the Flaviviridae family. Preventive vaccines and antiviral drugs are also considered. RT-PCR method is critical for confirmation of Zika fever diagnosis. ZIKV RNA may be detected in blood serum, saliva, amniotic and cerebrospinal fluids, urine, semen, vaginal and cervical secretions. The duration of viremia in case of Zika fever is short; therefore the presence of ZIKV RNA in urine and sperm for up to 26 and 80 days, respectively, extends the time interval for the detection of this pathogen. Detection of IgM antibodies by serological methods is not a good reason to confirm a recent infection, since antibodies of this class, specific to flaviviruses, circulate in the bloodstream for more than 12 weeks. The IgM show high diagnostic value in confirmation of congenital infection only. There is a problem of differential diagnostics of flavivirus infections caused by antigenically related viruses that are dangerous for humans, for instance, Dengue, Yellow fever, West Nile fever viruses, tick-borne and Japanese encephalitis viruses. It is associated with the similarity of their genomes and, consequently, similar antigenic structure of viral proteins, structural glycoprotein E in particular. More reliable results can be obtained by using the nonstructural glycoprotein NS1, produced by molecular biology methods, as an antigen for the detection of specific antibodies. This viral protein can also be used in serological tests, as a clinical indicator in case of acute Zika fever. Forty five types of candidate vaccines against ZIKV, such as inactivated, live attenuated, recombinant, peptide, recombinant DNA and RNA-based, virus-vector and virus-like particle ones were designed and studied. It was established that their protective efficacy is mediated by induced antibodies, specific to structural glycoprotein E which initiates receptor binding and fusion with the membranes of infected cells. Currently, there is no licensed preparation for treating patients with flaviviral infections. Various drugs are screened, both with known antiviral effect and approved for use in clinical practice, and new compounds that inhibit the penetration of viral particles into host cells (structural glycoprotein E being the target) and virus replication (targets are NS5, NS2B nonstructural proteins).

Keywords

• zika virus
• zika fever
• diagnostics
• candidate vaccines
• antiviral drugs