Chapter 20 - Systems multiple-molecule drug design in infectious diseases: Drug-design specifications approach

Abstract

Drugs fail in the clinic therapy for two main reasons; one is that they do not work and another is that they are not safe. As a result, two of the most important steps in developing new drugs should be the drug target identification and side-effect validation. The identification of drug targets and their restoration of cellular dysfunctions to normal cellular functions with less side effects are considered as drug-design specifications of systems medicine. Since the side effect on the normal expression of housekeeping genes and proteins is also considered as a restriction on systems drug design, the proposed multimolecular drug strategy might be helpful for systems drug design with less-side effects in the therapeutic treatment of infectious diseases. By systems biology method, host/pathogen genetic and epigenetic networks are constructed in this chapter to identify network biomarker for drug targets of infectious diseases by two-sided genome-wide high-throughput data. A computational network–based approach to investigate the pathogenicity and host-defensive mechanism for identifying multiple drug targets with drug data mining is also proposed for systems drug discovery of infectious diseases with more precise medicine and less side effects. Finally, some systematic drug-design specifications for drug design are proposed to repress pathogenic targets of disease and to restore to the normal functions of multiple drug targets of host with less side effects in the therapeutic treatment of infectious diseases. A systematic method is introduced to find multiple drug targets based on pathogenic mechanism and host-defensive mechanism investigated by network identification through host/pathogen two-sided genome-wide high-throughput data. Then a multimolecule drug-design strategy is also proposed to select a set of multimolecule drugs with less side effects for infectious diseases via drug data mining method. Systematic engineering design methods seem applicable to systems drug discovery and design for the therapeutic treatment of infectious diseases.