In silico designing and screening of lead compounds to NS5-methyltransferase of dengue viruses.
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.
Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur-613401, Tamil Nadu, India.
Dakshinamurthy
D
Sivakumar
Thirunavukkarasu
T
Sivaraman
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects* / Q000201:enzymology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C096041:NS5 protein, flavivirus; D017361:Viral Nonstructural Proteins; D012254:Ribavirin