Therapeutic Approaches for Zika Virus Infection of the Nervous System

Abstract

Zika virus has spread rapidly in the Americas and has caused devastation of human populations affected in these regions. The virus causes teratogenic effects involving the nervous system, and in adults and children can cause a neuropathy similar to Guillain-Barré syndrome, an anterior myelitis, or, rarely, an encephalitis. While major efforts have been undertaken to control mosquito populations that spread the virus and to develop a vaccine, drug development that directly targets the virus in an infected individual to prevent or treat the neurological manifestations is necessary. Rational and targeted drug development is possible since the viral life cycle and the structure of the key viral proteins are now well understood. While several groups have identified therapeutic candidates, their approaches differ in the types of screening processes and viral assays used. Animal studies are available for only a few compounds. Here we provide an exhaustive review and compare each of the classes of drugs discovered, the methods used for drug discovery, and their potential use in humans for the prevention or treatment of neurological complications of Zika virus infection.

Design, synthesis and in vitro anti-Zika virus evaluation of novel Sinefungin derivatives

“…Recently, SIN was demonstrated to show considerable anti-flavivirus activity (WNV, DENV-2 and YFV). Since ZIKV belongs to the flavivirus family, we agreed with others [13][14][15] in speculating that SIN might also be a potential ZIKV inhibitor. Scheme 1.…”

Importance of Zika Virus NS5 Protein for Viral Replication

“…This was achieved by Sofosbuvir's ability to disrupt the hydrogen bonding network inside the RdRp's active site thus leading to early chain termination. In addition, significantly higher A to G mutations were also recorded [63,69,70].…”

Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors

“…The genome of ZIKV encodes a polyprotein, which is then cleaved by cellular and viral proteases to form three structural proteins, including capsid (C), precursor of membrane/membrane (prM/M), and envelope (E), as well as seven nonstructural proteins, including NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 [8]. The life cycle of ZIKV involves several crucial steps, including viral attachment to target cell receptors or cofactors, receptor-mediated endocytosis (viral entry), virus–endosomal membrane fusion, and postentry or post-translation stages [9,10]. In this life cycle, E protein plays a key role in viral entry into target cells and subsequent fusion of virus and cell membranes; thus, ZIKV E protein serves as an important therapeutic target against ZIKV infection [11,12].…”