Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

Abstract

One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV), a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO) to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics), and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

Keywords: ZIKV research; Zika virus (ZIKV); computational drug discovery; current animal models; mosquito-borne flavivirus; novel molecular targets; vaccine development.

FIGURE 1

Structure of Zika virus (ZIKV). (A) Ultra structure of ZIKV with major surface proteins. (B) Genomic RNA of ZIKV exhibiting major structural and non-structural proteins. The crystal structure of available structural and non-structural protein of ZIKV. (C) The cryo-EM structure of ZIKV (PDB: 5IRE). (D) Structure of envelop protein (PDB: 5JHM). (E) Structure of NS1 protein (PDB: 5IY3). (F) Structure of the NS2b–NS3 complex (PDB: 5GXJ). (G) Structure of NS3 helicase (PDB: 5JPS). (H) Structure of NS5 protein (PDB: 5U0B).

FIGURE 2

The major events occurred in the replication and maturation of ZIKV inside the host cell followed by their release into the environment resulted in spread of the disease.

FIGURE 3

Various applications of animal models in ZIKV research included the study of pathogenesis and transmission, viral determinants and developments of vaccines and therapeutics.

FIGURE 4

The preventive action of Wolbachia spp. on ZIKV by cytoplasmic incompatibility (CI) to prevent transmission of disease. (A) The bacteria Wolbachia spp. infect the germ lines of mosquitoes and only female can transfer the bacteria to the next generation. The mating between bacteria infected males and uninfected females resulted in embryo lethality are known as CI, a major approach used to restrain insect populations in some pest-management systems. (B) CI may prevent in rescue mating between bacteria infected males and bacteria infected females. Because the effect of bacterial infection on the reproduction of insect supports the survival of bacteria infected females over uninfected females, bacteria might quickly spread during population of insect. (C) The bacterial infection can avert mosquitoes from being infected by some viruses that infect human host and the spread of the bacteria by an insect population is being used to prevent insect-mediated human diseases as per Sullivan and O’Neill (2017).

FIGURE 5

Schematic representation of the major concepts involved in the computational drug discovery of novel anti-Zika viral lead molecules. Drug discovery processes involved in the selection of novel and probable drug targets (both experimental structures and hypothetical models), selection of novel leads with ideal drug likeliness and pharmacokinetic properties, study of target-lead interaction by molecular docking, validation of the best docked poses by molecular dynamic simulation, selection of the best lead molecules, synthesis and large scale screening of the best leads and further experimental evaluation.