Discovery of novel drugs for treatment of dengue fever;2–o–methyl transferase as drug target.

Firdouse Nausheen; Shahnaaz; Bhargavi Chakrapani

Volume : IV, Issue : VI, June - 2015

Discovery of novel drugs for treatment of dengue fever;2–o–methyl transferase as drug target.

Firdouse Nausheen, Shahnaaz, Bhargavi Chakrapani

Abstract :

Dengue fever is an epidemic and the leading cause of illness and death in tropical and subtropical parts of the world (Centres for Disease Control and Prevention [CDC], March 2015). Every year approximately 400 million people are infected (CDC). So there is an urgent need to develop effective drugs for dengue. In this work, an attempt has been made on developing inhibitors for RNA cap (nucleoside–2‘–O–)–methyltransferase, an important enzyme required for replication of virus; thus preventing serious effects of infection. The target protein (1L9K) structure was downloaded from PDB and any inconsistencies in the sequence were checked and ruled out by BLAST p. Later we have screened ligands from Pub chem based on IC50(http://en.wikipedia.org/wiki/IC50)values and Lipinski rule of five (http://en.wikipedia.org/wiki/Lipinski%27s_rule_of_five). Their binding site on target was identified and binding energies have been calculated by AUTO DOCK .This resulted in different models having lowest binding energies for which pharmacophore models were designed by Discovery Studio 4.0 client. Later they were overlapped to build a robust pharmacon. Our results show that RNA cap (nucleoside–2‘–O–)–methyltransferase can be used as a potent drug target and our procedure may serve as a reference protocol for developing therapeutic strategies for emerging diseases.