Update on Methyltransferase Inhibitors of the Dengue Virus and Further Scope in the Field

Wangikar P, Martis EAF, Ambre

Abstract

Dengue virus (DENV) is extremely difficult to eradicate and the virus is responsible for a significant disease burden globally wherein several million people are mortally affected. In the quest for developing a treatment of this disease, scientists have described the methyltransferase (MTase) as a potential target. It is responsible for catalysing the methyl transfer from S-adenosyl-L-methionine that results in capping the mRNA at the N7 of a guanine and 2’-O of the first ribonucleotide. However, selectivity is the biggest challenge due to the presence of methyltransferases in humans. This review highlights key breakthroughs made in developing molecules against DENV MTase, and computational strategies that are employed to tackle the selectivity problem. We also present our perspectives on various unexplored and plausible computational techniques that can be employed to enhance tight binding and overcome the selectivity issues.