Drugs to limit Zika virus infection and implication for maternal-fetal health

Abstract

Although the placenta has robust defense mechanisms that protect the fetus from a viral infection, some viruses can manipulate or evade these mechanisms and disrupt physiology or cross the placental barrier. It is well established that the Zika virus is capable of vertical transmission from mother to fetus and can cause malformation of the fetal central nervous system (i.e., microcephaly), as well as Guillain-Barre syndrome in adults. This review seeks to gather and assess the contributions of translational research associated with Zika virus infection, including maternal-fetal vertical transmission of the virus. Nearly 200 inhibitors that have been evaluated in vivo and/or in vitro for their therapeutic properties against the Zika virus are summarized in this review. We also review the status of current vaccine candidates. Our main objective is to provide clinically relevant information that can guide future research directions and strategies for optimized treatment and preventive care of infections caused by Zika virus or similar pathogens.

Discovery And Characterization of Small Molecule Inhibitors of Zika Virus Replication

“…Identifying a specific target is vital in screening a lead compound that may function as an inhibitor. Many inhibitor candidates have shown the ability to target viral proteins, including the envelope, protease, helicase, and polymerase (33). Among them, viral protease seems to be an attractive target due to its critical role in the proteolytic cleavage of the polyprotein, inhibiting the further onset of the viral replication life cycle.…”

“…In this context, many inhibitors have also been identified that can potentially block NS2B-NS3 protease activity and, in turn, have the potential to inhibit ZIKV replication (34,(51)(52)(53). In addition, other drugs have also shown potential as ZIKV inhibitors by different means (33).…”

“…Many previous pieces of literature warrant investigation of inhibitors of ZIKV that have the potential to target both entry and post-entry steps (33). Such inhibitors have been reported to inhibit viral entry to the host cell by targeting receptor binding, fusion, and endocytosis steps (33,(54)(55)(56)(57)(58).…”

“…Many previous pieces of literature warrant investigation of inhibitors of ZIKV that have the potential to target both entry and post-entry steps (33). Such inhibitors have been reported to inhibit viral entry to the host cell by targeting receptor binding, fusion, and endocytosis steps (33,(54)(55)(56)(57)(58). Further testing of these compounds is needed to investigate the detailed insight into the mechanism of action and its inhibition potential using in vivo model systems.…”

“…In contrast to many prior approaches that have explored the use of repurposed drugs (33), our objective here is to discover novel compounds that could target NS3 or NS5 to inhibit ZIKV replication. To achieve this, we took a computational drug discovery approach using docking and simulation coupled with further in vitro validation using virological assays.…”