Chapter 13 - Zika Virus Polymerase: Structure, Function, and Inhibitors

Abstract

Among the human infections transmitted by mosquito, Zika virus (ZIKV) infection has potential as worldwide pandemic. ZIKV infection can spread from person to person vertically from mother to fetus or through sexual contact and thus differs from other pathogenic flaviviruses. ZIKV infection is asymptomatic and has been strongly associated with neurological sequelae (Guillain–Barre syndrome), meningoencephaitis, and myelitis. During pregnancy ZIKV infection may cause dreaded complications leading to fetal abnormalities and death. Currently no specific therapies or vaccines are approved for prevention and treatment of ZIKV infection. ZIKV structure has been revealed that shows remarkable similarities with those of other flaviviruses. Inhibition of viral MT activity and/or RNA synthesis can be developed for inhibiting ZIKV replication. Various ZIKV proteins complexed with inhibitors could aid in accelerating the drug discovery process. The consequences of ZIKV mutations suggest the urgent need for viral inhibitors with higher specificity and potency. Rationalized approaches are fundamental in the discovery of potent inhibitors to mask the virus as well as its destruction. The advent of in silico drug design allows rapid screening of potential leads and reduces the consumption of time and resources. Various optimized and proven screening techniques and their results in the discovery of potential inhibitors of ZIKV methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRP) have been elaborated.