In silico Designing and Screening of Lead Compounds to NS5-Methyltransferase of Dengue Viruses

Dakshinamurthy      Sivakumar; Thirunavukkarasu      Sivaraman

doi:10.2174/157340611797928451

Abstract

Ribavirin and its 553 analogues have been docked with NS5-methyltransferase of Dengue viruses using Glide- HTVS and Glide-XP computational tools and the compounds have been screened based on their Glide-Gscores to identify lead ribavirin analogues that may act as inhibitors to the enzyme. Upon studying the interactions of ribavirin triphosphate (RTP) and triphosphate of lead ribavirin analogues with NS5-methyltransferase and Janus tyrosine Kinase-2 (JAK2) enzymes using molecular docking and dynamic methods, the possible mechanism by which the ribavirin causes haemolytic anaemia has been proposed. De novo RTP-analogues showing stronger affinities with NS5-methyltransferase and weaker affinities with JAK2 have been designed. The essential structural features of the de novo RTP-analogues for developing them as specific antiviral drugs against the infections due to dengue viruses have been discussed in detail.

Keywords: Drug design, glide-HTVS, JAK2, molecular docking, NS5-methyltransferase, ribavirin, haemolytic anaemia, RTP-analogues, Dengue viruses, Glide-Gsc