Abstract
Neuraminidase (NA) is the major surface protein of the influenza virus. It extracellularly acts by cleaving the terminal neuraminic acid from cellular receptors recognized by the Hemagglutinin. Then, it facilitates the release of newly formed visions from the host cell surface to the neighboring cells, thereby facilitating the spread of the virus. A 150-cavity adjacent to the active conservative site is possessed by the group-1 neuraminidase, thereby rendering conformational change from open to close form when the ligand binds to the enzyme. In the present study, we reported an in silico virtual screening and docking analysis for potential neuraminidase inhibitors of various ligands obtained from the ZINC database using Autodock Vina against the 3TI6 protein. Analysis of 850 screened ligands reveal that five compounds with free binding energies of -11.2, -10.9, -10.4, -10.4, and -10.1 kcal/mol (ZINC03260201, ZINC09153352, ZINC09460395, ZINC13128611, and ZINC20605436, respectively) showed interaction with the protein at the known active site, as well as with the 150-cavity creating a stronger interaction between the ligand and the protein. Furthermore, lower binding energy is exhibited compared with the co-crystallized drug oseltamivir. In silico absorption, distribution, metabolism, and excretion (ADMET) prediction revealed that best compounds show comparative results with oseltamivir. Novel compounds interacting with the 150-cavity were successfully identified using this approach; such compounds could serve as a potential lead compound for developing a new anti-neuraminidase drug.
Highlights
Influenza A virus is considered a serious health problem because of the annual morbidity and mortality caused by this disease (Couch et al, 1996)
Author reported an in silico virtual screening and docking analysis for potential neuraminidase inhibitors of various ligands obtained from the ZINC database using Autodock Vina against the 3TI6 protein
Ligands screening from ZINC database The three dimensional structure of 850 ligand molecules were retrieved from ZINC database (Irwin and Shoichet, 2005) in mol2 format, the ligands converted to pdbqt using raccoon (Forli et al, 2016)to be used for virtual screening with AutoDock Vina
Summary
Influenza A virus is considered a serious health problem because of the annual morbidity and mortality caused by this disease (Couch et al, 1996). Hemagglutinin (HA) and neuraminidase (NA), are attached to the influenza virus. The role of hemagglutinin is to help the virus attach to and penetrate the host cell via sialic acid (SA) binding sites (Couceiro et al, 1993; Wileyand Skehel, 1987), whereas the neuraminidase (NA) role is to cleave terminal sialic acid residues between cleaved terminal sialic acid residues. This finding mainly explained why NA is taken as a drug target for developing agents in influenza drug discovery. Current treatment exists for influenza infections with the newer class of neuraminidase inhibitors, such as zanamivir (Relenza) and oseltamivir (Tamiflu) (Von Itzstein, 2007; Xu et al, 2008)
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