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Millions of experimental animals are widely used in the assessment of toxicological or biological effects of manufactured nanomaterials in medical technology. However, the animal consciousness has increased and become an issue for debate in recent years. Currently, the principle of the 3Rs (i.e., reduction, refinement, and replacement) is applied to ensure the more ethical application of humane animal research. In order to avoid unethical procedures, the strategy of alternatives to animal testing has been employed to overcome the drawbacks of animal experiments. This article provides current alternative strategies to replace or reduce the use of experimental animals in the assessment of nanotoxicity. The currently available alternative methods include in vitro and in silico approaches, which can be used as cost-effective approaches to meet the principle of the 3Rs. These methods are regarded as non-animal approaches and have been implemented in many countries for scientific purposes. The in vitro experiments related to nanotoxicity assays involve cell culture testing and tissue engineering, while the in silico methods refer to prediction using molecular docking, molecular dynamics simulations, and quantitative structure–activity relationship (QSAR) modeling. The commonly used novel cell-based methods and computational approaches have the potential to help minimize the use of experimental animals for nanomaterial toxicity assessments.

Human epidermal growth factor receptor 2, HER2, is a commonly over-expressed tyrosine kinase receptor found in many types of carcinoma. Despite that there are several HER2 inhibitors, namely Iressa, Tarceva and Tykerb, currently in clinical trials, all can cause several side effects. In this study, both structure-based and ligand-based drug design were employed to design novel HER2 inhibitors from traditional Chinese medicine (TCM). The HER2 structure model was built in homology modeling based on known receptors of the same family. Docking and de novo evolution experiments were performed to identify candidates and to build derivatives. A training set of 32 compounds with inhibitory activities to HER2 was used to formulate the pharmacophore hypotheses that were subsequently used to examine candidates obtained from the docking study. Hydrogen bond interactions, salt-bridge formations and pi-stacking were observed between the ligands and Phe731, Lys753, Asp863 and Asp808 of HER2 protein. Combining results from both docking and pharmacophore mapping analysis, CLC015-5, CLC604-11 and CLC604-18 were well accepted and consistent in both approaches and were considered as the most potential HER2 inhibitors.

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.