In silico study of guanosine triphosphate (GTP) and ribavirin derivatives as the inhibitor for NS5 methyltransferase of dengue virus

Dengue virus (DENV) infection has become a major health threat lately, endangering at least one-third of world’s population and infecting 100 million people each year. Thus, these problems can be overcome by finding new solutions to control the DENV contagion level are needed, and one of them can be achieved by finding new drugs. Ribavirin and guanosine triphosphate (GTP) derivatives can be used as an antiviral drug design for this disease, especially in inhibition of enzymatic activity of the methyltransferase (Mtase) that involves in synthesizing DENV cap-RNA. In this study, we used the in the silico study through molecular docking simulation using AutoDock Vina 1. 0 and MOE 2008. 10 software. In addition, the toxicity and synthetic accessibility prediction were conducted as well. The results show the modified ligand derivatives of GTP and RTP, such as viramidine, xanthosine, and inosine, have favorable inhibition activities in the DENV NS5 Mtase in terms of the binding affinity and their interactions with the important residues of the DENV NS5 Mtase active site. Moreover, these ligands also have good drug properties as well. As the conclusion, the viramidine, xanthosine, and inosine derived ligands can be developed as a lead candidate as DENV NS5 MTase inhibitors for dengue fever therapy.