Target-based drug discovery for the development of novel antiinfectives

• Published in: International journal of medical microbiology Vol. 290; no. 2; pp. 191 - 201
• Main Authors: Selzer, Paul M., Brutsche, Sandra, Wiesner, Petra, Schmid, Peter, Müllner, Hubert
• Format: Journal Article
• Language: English
• Published: Jena Elsevier GmbH 01.05.2000; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - drug effects; Bacteria - genetics; Bacteria - metabolism; Bacterial Infections - microbiology; Bacterial Proteins - drug effects; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological and medical sciences; Biotechnology; Computational Biology; Drug Design; Fundamental and applied biological sciences. Psychology; genomics; Genomics - methods; Health. Pharmaceutical industry; high-throughput screening; Humans; Industrial applications and implications. Economical aspects; infectious disease; Medical sciences; microorganism; Pharmacology. Drug treatments; Production of active biomolecules; resistance; virtual screening; microorganism; genomics; virtual screening; infectious disease; resistance; high-throughput screening; Genomics; Review; In vitro; Antimicrobial agent; Research and development; Resistance; Screening; Antibiotic; Targeted drug; Antiinfectious; Microorganism; Bioinformatics; Medical application; Computer aided analysis
• ISSN: 1438-4221; 1618-0607
• DOI: 10.1016/S1438-4221(00)80090-9

In the 20 th century and especially during the last 50 years, antiinfectives have been increasingly used to control and prevent infectious diseases. Unfortunately the resistance of microorganisms to these Pharmaceuticals has increased as well. At the same time the discovery process for novel antiinfectives, the so-called “conventional” screening approach, involves testing natural products or derivatives of known compounds in in vitro cultures. By now it is obvious that this screening approach did not meet the expectations to generate a sufficient number of novel drug candidates. Consequently, studies for selective antiinfectives with new modes of action, which are able to break resistance, are highly desirable for human and animal health. The enormous advance in sequencing technologies — leading to a constantly growing number of known microbial genomes — together with the rapid development of computer power and bioinformatic software tools, now makes it possible to identify genes and gene products that are essential to the pathogenic organisms and are therefore considered to be novel targets for the development of new antiinfectives. When these potential targets have been validated by sophisticated laboratory methods, large diverse compound libraries can be tested in in vitro assays using high-throughput screening. This approach will most likely generate an increasing number of novel lead structures that will be specifically optimized by modern combinatorial chemistry and subsequently lead to new antiinfective candidates strengthening the armoury of weapons available to fight infectious diseases in humans and animals.