Characterization of Dengue virus 3 Untranslated region 3UTR as potential drug target

Abstract

Dengue virus infections are recorded as hyper-endemic in many countries, including newlineIndia. Research pertaining to the reasons for frequent outbreaks and severe dengue is ongoing. newlineWith four different strains circulating over the past few decades globally, characterization at newlinethe molecular level of these strains is a prerequisite to analyse the serotype/genotypes pattern newlinechange, emergence of new strains and their virulence which includes sequencing of the entire newlinegenome or gene fragments. As viruses seize the host environment for their replication and newlinesurvival, it associate with many host proteins and receptors whose role has not been deciphered. newlineSo, the main aim of the present study was to characterize the dengue strains with main focus newlineon the 3 Untranslated region (3 UTR) as well as interacting host proteins and investigate their newlinerole for developing the anti-dengue therapeutics. We observed changes in the serotype newlinedominance as well as genotype change for DENV1 in Hyderabad, which is our place of study. newlineFurther, 3 UTRs of DENV1and2 were further amplified and sequenced where deletions in both newlineDENV1and2 were observed and further analysis showed association of these strains with disease newlineseverity. We also analyse the interacting proteins with the 3 UTR and found MYH9 or newlineNMMHC IIA (coded by the gene Myh9) protein bind to the 3 UTR. This protein was found to newlineinteract with the dengue virus envelope protein. Hence, MYH9 appears to play a dual role newline(entry and replication) in dengue virus pathogenesis, initially by acting as novel receptor during newlineearly stage of infection and facilitating virus replication in the later stages by involving in newlinereplication complex formation. Further, we investigated on inhibitor (ML-7) against MYH9 newlineprotein, which showed good therapeutic potential against dengue.