Brain grants permission of access to Zika virus but denies entry to drugs: a molecular modeling perspective to infiltrate the boundary

Abstract

The magnetism of the Zika virus to neuronal cells proves to be one of the major concerns in the development of effective inhibitors. Although the blood–brain barrier limits the entry of most drugs, tailored small molecule inhibitors and drug delivery systems are currently being designed to overcome this obstacle. We have identified the core challenge to be addressed – blood–brain barrier permeability – and provided insight into strategies that can be used to improve drug delivery to the brain. We have compiled drugs that have previously been proposed as potential Zika virus inhibitors and classified chemical features of those drugs, which influence blood–brain barrier permeability. Thereafter, we created a route map to design drugs with improved blood–brain barrier permeability. An alternative approach using drug delivery systems to transport membrane-impermeable Zika virus inhibitors to the brain is also proposed, along with descriptions of known drug carriers. This review provides information for further research toward inhibitors of Zika virus.