In silico screening of alkaloids and terpenoids as inhibitors of avian influenza neuraminidases (N2 and N9)

Date

5-2007

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Ernesto J Del Rosario

Co-adviser

Jelynne P. Tamayo

Committee Member

Katherine Ann C. Israel

Abstract

Influenza A is a major human sickness; the virus continuously replicates and shows resistance to anti-viral drugs. In the advent of modern technology, the design of new broad spectrum anti-influenza drugs by molecular modeling and structure based approaches is becoming more important. Neuraminidase (NA) is a surface glycoprotein of influenza virus being targeted for inhibition. It is critical for viral release from the infected cells and viral transport in the respiratory tract. AUTODOCK 3.05 software was used to study the binding of naturally occurring alkaloids and terpenoids to neuraminidases N2 and N9. The accurate prediction of protein-ligand binding energy is a key goal for efficient drug design. Prior to docking the alkaloids and terpenoids, control docking was done in order to validate the method of Autodock and the binding site of neuraminidases N2 and N9. The binding site was validated by binding 3-Amino-4-(acetylamino)-5-hydroxybenzoic Acid Hydrochloride (BANA 106) to N2 and 4-guanidino-Neu5Ac2en (GANA) to N9. Alkaloids and terpenoids were docked to the N2 and N9 enzymes and the free energies of binding were calculated. Results showed among the alkaloid compounds ATI 0 and ascididemin1 bind with N2 and N9 more effectively than the others. On the other hand, among the terpenoid compounds hopane bind to N2 and N9 more efficiently than the others. Oseltarnivir and Zanamivir, commercial drugs against influenza virus and known to be good inhibitors, were also docked to N2 and N9 and were observed to bind to the active site. Based on the results obtained there are some ligands that bind in the enzymes N2 and N9 more effectively. Among the compounds that were docked to N2, all of the terpenoids and AT9 had more negative binding energies than the known inhibitors. On the other hand, among the compounds docked to N9. ascididemin1, ascididemin2, AT10, anotoxane and hopane gave the more negative AG,„,,,(Appendix I).

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2007 C4 G85

Document Type

Thesis

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