As a leading service provider in the field of biological research and drug discovery, Creative Biolabs has designed a complete and thorough protocol to explore the potential and well-recognized targets based on the diverse technology platforms such as whole genome sequencing (WGS), gene manipulation, and phage display. Our professional team is confident to provide our clients with a range of antifungal drug discovery services, including target identification and validation, Hit identification, Hit to lead, Lead optimization, and IND enabling to meet the novel drug discovery goals.
How to Find Antifungal Drugs?
Fungal diseases are often caused by fungi that are common in the environment. When the body‘s immune system is weakened, or the body’s flora is unbalanced, pathogenic fungi can easily infect the body and cause disease. An antifungal drug that is designed to selectively against the essential molecules of fungi structure or key enzymes during fungi metabolic activity thereby suppress fungi growth while minimal or no toxicity to the mammalian host. However, fungus, like humans, both belong to eukaryotes whose cells are mainly composed of cell membrane, cell wall, and cell nucleus, thus making it difficult to develop antifungal drugs. Currently available antifungal agents may be categorized according to their molecular targets. Primary molecular targets for antifungal agents are enzymes and other molecules involved in cell wall synthesis, plasma membrane synthesis, fungal DNA and protein synthesis, cellular function-related, and virulence factors.
Fig.1 Molecular architecture of the fungal cell wall and membrane of Candida albicans. (Mccarthy, 2017)
Potential Targets for Antifungal Drugs
The cell wall is a very essential structure of fungi and absents from the mammalian host. Hence fungi cell wall provides an important target for developing fungal-specific drugs. The components of fungi cell wall or important regulatory enzymes involved in cell wall synthesis are both regarded as the targets for antifungal drugs. Now studies have reported a number of fungal-specific drug targets associated with synthesis of fungi cell wall, such as targets involved in glucan biosynthesis, glycosylphos-phatidylinositol (GPI) biosynthesis, chitin biosynthesis, mannoprotein biosynthesis.
Ergosterol is one of the components of fungal cell membrane and not the components of mammalian cell membrane. So the drugs against ergosterol or key enzymes in the ergosterol synthesis process can effectively suppress fungal cell growth without effect on mammalian cells. Besides, glycosphingolipids (GSLs) are a kind of glycolipid that are found in fungi cell membranes regulating pathogenicity in a variety of fungus. Proton ATPases on fungi cell membranes is very important for fungal growth. Hence these molecules both become the target of antifungal drugs.
Some molecules such as protein elongation factors (EF2), N-myristoyltransferase (NMT), isoleucyl-tRNA synthase exert a necessary function in nucleic and protein biosynthesis of fungi. Hence these molecules are also regarded as the targets for antifungal drugs.
Fig.2 Current and future therapies for cryptococcosis. (May, 2015)
It is known that molecules or signal pathways especially related to fungal cellular function is very important for fungus growth. These molecules also can be considered as the potential targets for antifungal drugs. For example, mitogen-activated protein kinase (MAPK) pathway is a network of signaling pathways that allow adaptation to environmental changes and is evolutionarily conserved from yeasts to mammals. The divergent point between fungal and mammalian MAPK pathways is their upstream signaling module. Based on this, several MAPK signaling pathways in fungi have been identified which may have therapeutic implications: the Mkc1 pathway, the Cek1 pathway, the Cek2 pathway, and the high-osmolarity glycerol (HOG) pathway.
Virulence factors produced by the fungi are necessary for causing disease in the host and determine the degree of pathogenicity. They are important for fungi in the ability to grow at physiological temperature and pH. Therefore, antifungal drugs also enable to be developed against virulence factors to suppress fungi growth.
Advantages in Creative Biolabs
Creative Biolabs has years of experience in the drug targets discovery including antifungal drugs. Not only the technology platform but also the experienced team can support our global clients attain their interested drug target from the extensive repertoires of antifungal drug targets. We also believe that you may attain the yield twice the result with half the effort with our assistance. Please contact us for more details or a detailed quote.
References
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