Ligand-based dual target drug design for H1N1: swine flu--a preliminary first study.
In March and April, 2009, an outbreak of H1N1 influenza in Mexico had led to hundreds of confirmed cases and the death toll had risen to 160. The worldwide spread of H1N1 has been attracting global attention and arising an overwhelming fear. So far, the vaccine and remedy has been in urgent need. In this study, a QSAR model and pharmacophore map of neuraminidase (NA) type 1 (N1) contained two hydrogen bond acceptor features, one hydrogen bond donor feature, and one positive ionizable feature. NCI database was employed in virtual screen by the N1 pharmacophore map features. After screening, compounds were obtained and then docked into haemagglutinin type 1 (H1) to find out the candidate drugs for dual target of both N1 and H1. The candidate, NCI0353858, selected via virtual screening and docking, might be functional to this worldwide disease; consequently, further clinical investigations and scientific application are urgently demanded. We realize the proposed ligand does not have much validity without conducting a study on the stability of the protein-ligand complex by MD simulations and binding free energy, and such a study is underway and will be reported later in this journal. Nevertheless, the present study is clear, consistent and could give a rational explanation for the binding mode of the best selected ligand.
Chen
Chien-Yu
CY
Laboratory of Pharmacoinformatics and Nanotechnology Department of Biological Science and Technology, China Medical University Taichung, 40402, Taiwan.
Chang
Yea-Huey
YH
Bau
Da-Tian
DT
Huang
Hung-Jin
HJ
Tsai
Fuu-Jen
FJ
Tsai
Chang-Hai
CH
Chen
Calvin Yu-Chian
CY
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy / Q000517:prevention & control; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013552:Swine; D014612:Vaccines
D000998:Antiviral Agents; D008024:Ligands; D014612:Vaccines