Ligand-Based Dual Target Drug Design for H1N1: Swine Flu- A Preliminary First Study

Abstract

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.

Drug design for hemagglutinin: Screening and molecular dynamics from traditional Chinese medicine database

“…different topics (Bhargavi et al, 2010;Cambria et al, 2010;Cao and Wang, 2010;Chang et al, 2010;Chen, 2010;da Cunha et al, 2010;Huang et al, 2010a,b;Kahlon et al, 2010;Koshy et al, 2010). Previously, we had conduced in silico studies on influenza hemagglutinin (Chen et al, 2009a. As a continuation, we performed molecular dynamics simulation to further investigate ligand-H1 interaction.…”

“…As a continuation, we performed molecular dynamics simulation to further investigate ligand-H1 interaction. In the past, we have successfully conducted drug design by combining traditional Chinese medicine (TCM) and both ligand-based and structural-based drug design (Chen et al, 2009aHuang et al, 2010a,b,c). We hope new success can be discovered by employing TCM on treating H1N1 infection.…”

Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5

“…In addition to receptor-based docking study, ligand-based multiple linear regression was also used in this study [15][16][17][18]. Combination of receptor-based and ligand-based methods to improve reliability of, a large number of putative inhibitors of PDE-5 were screened [19][20][21].…”

Potential Retinoid X Receptor Agonists for Treating Alzheimer’s Disease from Traditional Chinese Medicine

“…Previously to in silico drug discovery researches, many compounds extracted from traditional Chinese medicine (TCM) have been indicated as potential lead compounds used for wide range of diseases, including metabolic syndrome [34–36], stroke [37–40], cancers [41–45], influenza [46–49], viral infection [50], diabetes [51], inflammation [52], and some other diseases [53, 54]. To improve drug discovery from TCM compounds, we aim to investigate the potent candidates as RXR agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan.…”