Drug Discovery: Uncovering New Antifungal Drugs - Essay Example

Review of group report: Case study on drug discovery – uncovering new antifungal drugs Summary of the main points covered The report provides an overview of the antifungal drug therapies that are currently in use. It states the current need for new therapy in view of the fact that there are more incidences of fungal infections. The need for newer drugs is more urgent with the advent of new diseases like HIV, and medical advances such as organ transplantation, chemotherapy, and burn treatment. Special patients from these events are immune-compromised and are more prone to fungal infections either at the hospital or in their homes. New effective antifungal drugs are absent and the standard of treatment remains Amphotericin B which was discovered more than 50 years ago, and is toxic to the host organism. Current drugs and their targets are described briefly, and then the report tackles alternative treatment like natural products, and the use of modern technologies to study fungal genetics, identify new targets, and improve drug-target binding. Strengths The report is able to provide an overview of the current state of knowledge on antifungal drug therapy. It identified the rationales for developing new antifungal drugs, which are increased incidence of fungal diseases, and a new class of special immune-compromised patients. Furthermore, the report accurately pointed to selective targeting as a major problem in drug design brought about by similarities in the genetic make-up of fungi and man. Because of this similarity, antifungal drugs target the host cells too, which account for drug toxicity, identified to be one of the major challenges in drug design. Limitations posed by the present drugs were described, setting the background for the ensuing discussion. Recent directions in drug development were also presented with respect to the approach used, and the possible modes of drug action. The availability of the genome sequences of humans and yeast paved the way for advances from using genomic tools like mutants, gene microarrays, and transcript profiles, to exploiting the immune response. Current limitations with these studies were identified and the conclusion was that new agents are still to be derived using the genomic and molecular approaches. The report highlighted advanced work on the identification of new cell wall targets, development of novel drug derivatives, and modification of existing drugs based on results of structural analysis. Weaknesses Despite the amount of information that the report gave, it has some weaknesses especially in discussing the strengths and advantages of the new techniques used. A very important consideration in drug design is the type of administration of the drug. The paper failed to mention that there were two types of antifungal drugs: systemic and topical. The discussion only on systemic drugs, although there are important fungal infections (e.g. dandruff) that require topical applications. Toxicity can be an issue, not only for systemic, but also for topical applications. The report also failed to specifically point out that despite similarities between humans and fungi cells, key differences exist at the cellular level like the presence of cell wall in the fungi, and cholesterol not being present in the cell membrane (Merck Co., 2001), which served as targets for drug intervention. A very significant weakness of the paper was its inability to present cohesively the information on the genomics work. This was loosely presented, and the train of ideas does not show a definite direction of the studies. There was, basically, just a listing of techniques, quite lacking an in-depth analysis of the advantages over traditional approaches in drug design. More importantly, the advantages on the use of genetics for understanding growth of the most common infective pathogens (De Backer, et al., 2001) were not emphasized. Understanding the biological basis of infection and its many complex pathways is actually the main goal of all anti-drug therapies. A limitation of the report was its inability to discuss was the development of drug resistant fungal strains, a primary consideration in designing new generation drugs. Many drug resistance mechanisms have been identified, and these were associated with azoles and derivatives (Sanglard, 2003). Alterations in ergosterol biosynthesis and drug targets are responsible for resistance and the report failed to show what current work deal with these. The design of drugs that enhance the action of another or the exploitation of multi-drug therapy was an aspect that the report failed to discuss. Many difficult to manage infections are dealt with a combination of drugs to escape development of drug resistance and to improve the treatment efficacy (Onyewu & Heitman, 2007). Most antifungal drugs inhibit the synthesis of ergosterol but do not kill the fungus. This property of the drug encourages the emergence of fungal species that are drug resistant. Other very effective drugs produce toxic effects if given continuously and need to be administered intravenously. These are not characteristics of ideal fungicidal drugs. To offset the undesirable effects of traditional antifungal medicine, unrelated drugs can screened for beneficial interaction. The combination can be applied to effectively kill the fungal cells (Onyewu & Heitman, 2007). Such drug interactions can be screened for use for the pathogens with developed drug resistance. The conclusion of the report is quite brief and describes the ideal antifungal drug, with due consideration given to immune-suppressed patients. There were no justification why these was the conclusion arrived at. The report also failed to give recommendations, based on the study conducted, on what direction must be taken by the researcher or clinician who wants to design novel and effective antifungal drugs. A good conclusion would have been to make use of genomic technologies, which are more high throughput and give an understanding of pathogen-host relationship, to improve and modify known traditionally effective antifungal drugs like the polyenes and the azoles. Reason for choosing this report over the other reports Although all have interesting topics, this report was chosen because it was very different from the report on anti-HIV drug therapy, which was submitted by our group. Problems with fungal diseases have not been getting as much attention compared to those of viruses and bacteria. Therefore, its nature was less familiar to me as a student and this report gave me a good opportunity to learn something novel. References De Backer, M., Nelissen, B., Logghe, M., Viaene, J., Loonen, I., Vandoninck, S., et al. (2001). An antisense-based functional genomics approach for identification of genes critical for growth of Candida albicans. Nature Biotechnology, 19:235-241. Merck Co. (2001). Introduciton to Medical Mycology. Onyewu, C., & Heitman, J. (2007). Unique applications of novel antifungal drug combinations. Anti-Infective Agents in Medicinal Chemistry, 6:3-15. Sanglard, M. (2003). Resistance to Antifungal Drugs. In W. Dismukes, P. Pappas, & J. Sobel, Clinical Mycology (534 pages). New York: Oxford University Press. Read More