Potential targets for therapeutic intervention and structure based vaccine design against Zika virus

Abstract

Continuously increasing number of reports of Zika virus (ZIKV) infections and associated severe clinical manifestations, including autoimmune abnormalities and neurological disorders such as neonatal microcephaly and Guillain-Barré syndrome have created alarming situation in various countries. To date, no specific antiviral therapy or vaccine is available against ZIKV. This review provides a comprehensive insight into the potential therapeutic targets and describes viral epitopes of broadly neutralizing antibodies (bNAbs) in vaccine design perspective. Interactions between ZIKV envelope glycoprotein E and cellular receptors mediate the viral fusion and entry to the target cell. Blocking these interactions by targeting cellular receptors or viral structural proteins mediating these interactions or viral surface glycans can inhibit viral entry to the cell. Similarly, different non-structural proteins of ZIKV and un-translated regions (UTRs) of its RNA play essential roles in viral replication cycle and potentiate for therapeutic interventions. Structure based vaccine design requires identity and structural description of the epitopes of bNAbs. We have described different conserved bNAb epitopes present in the ZIKV envelope as potential targets for structure based vaccine design. This review also highlights successes, unanswered questions and future perspectives in relation to therapeutic and vaccine development against ZIKV.

Keywords: CRISPR Cas9; Entry inhibitor; Envelope proteins; Epitopes; Glycans; Lectins; NS1; NS5; Protease inhibitors; Structure-based vaccine; Therapeutic targets; Vaccine targets; Zika virus.