In Silico Analyses; Inhibition of the Selected Pathogenic Proteins of Zika and Ebola Viruses

Abstract

The catastrophe Zika virus infused in South America including Brazil and other Caribbean countries obliterated the lives and health of the inhabitants. The neonatal health was badly infected as microcephaly come out the distinctive character of this grave viral attack. The need of the hour is to dive deep in the melancholy and find out robust scientific and advanced techniques both horizontally and vertically which ward off the next generations interim of antiviral drugs and preemptive measures. Due to congenital microcephaly and Guillain-Barre syndrome in human, Zika virus has been gaining attention from scientists. The Zika virus is amongst Flaviviruses like Dengue virus, Japanese encephalitis, Yellow Fever virus, Thick Warm virus and West Nile virus. These are mosquitoes borne human pathogens specially species Aedes aegypti. There are numerous proteins responsible for the pathogenesis of virus including seven of the NS proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) which are integral part of replication complex, located at the cytoplasmic side of the endoplasmic reticulum membrane. Among these proteins three were selected as drug targets to halt virus infections. Availability of the X- ray crystal structures of Zika virus proteins enabled structure based drug design efforts. First drug target was lipid containing glycosylated NS1 that makes a homodimer inside the cells while its secretion take place inside the extracellular space as hexameric lipoprotein. This leads to the evasion of immune system and causes pathogenesis through establishment of interaction with components from both innate and adaptive immune system as well as other host factors. The second drug target was NS3 helicase protein triggered pathogenesis through replication of RNA and it depends upon ATP. NS3 is one of the most thoroughly studied antiviral drug targets. The enzymatic activity is coupled with the C-terminal region of the nonstructural protein NS3 in Flaviviruses, namely an RNA helicase (NS3-Hel) concerned in genome replication and RNA synthesis. The third target was NS5 protein which is distinctive among other RNA viruses because it contains a fused domain composed of two terminals an Nterminal RNA methyltransferase (MTase) domain and a C-terminal RNA-dependent RNA polymerase (RdRp) domain. The N-terminal MTase domain is responsible for 5′capping and thereby stabilizes the viral RNA genome, while the C-terminal RdRp domain is critical for viral RNA replication and beleaguered for inhibition.