Pustaka Ilmiah Universitas Padjadjaran

Abstrak

VIRTUAL SCREENING ON NEURAMINIDASE INHIBITORS ACTIVITY OF PLANT- DERIVED NATURAL PRODUCTS BY USING PHARMACOPHORE MODELLING AND DOCKING

Neuraminidase (NA) plays an important role in the replication and release of new avian influenza virion. Due to this event, NA had been considered as a valid target in drug design against influenza virus. The aim of this study is to identify the new neuraminidase inhibitors, using pharmacophore modeling and docking based virtual screening from natural compounds of Malaysia. A variety of natural compounds from plant sources of Malaysia which collected in NADI database has been screened to possess substantial neuraminidase inhibitors properties. Pharmacophore model was developed using Catalyst software embedded in Discovery Studio 2.1 by using sialic acid derivatives which act as N1 inhibitors. The pharmacophore hypothesis selected had five features (one hydrogen bond donor (D), one negative ionizable (N), one positive ionizable (P), and two bond donor (D), one negative ionizable (N), one positive ionizable (P), and two hydrophobic moiety (Hy), also included two excluded volume. Best pharmacophore was validated by Hyporefine in DS 2.1 which has a lowest total cost value (92.055), the highest cost difference (107.807), the lowest RMSD (1.197), and the best correlation coefficient (0.944651)..The X-ray crystal structure of Neuraminidase N1 (1F8B) was used in the docking studies, using Autodock 3.0.5 software, and the free energy of binding was used to rank the hits, whereas oseltamivir and DANA have been used as the ligands in controlled docking. In silico screening had been carried out on the compounds of our laboratories database (NADI). The mapping of NADI database natural compounds shows that 46 compounds of 2350 NADI compounds map to three feature of common pharmacophore training set. MSC458 (Morinda citrifolia) have the highest fit value with free energy docking -9.48 kcal/mol (Ki 1.12x 10-7) into neuraminidase, whereas MSC605 have the most negative free energy of bind (-12.10) and Ki 1.35x 10-9.