Coccidioidomycosis

= Disease: __Coccidioidomycosis__ =

Motivation and Background:
Coccidioidomycosis, also known as Valley Fever, is a fungal disease spread by the inhalation of spores [6]. The fungus, Coccidioides, that causes this disease can be found in the soil in the Southern/Western portion of the United States, including Texas [2]. The fungus spreads past the border into Mexico, Central America and South America. There are two different types of fungi that can cause the disease, Coccidioides immitis and Coccidioides posadasii [2]. Most often the fungus spores are inhaled and the disease is transmitted but sometimes the fungus can enter the body through cuts or wounds in the skin. This disease is most commonly found in patients with weak immune systems and adults who are over the age of sixty. Because this disease is gained from the fungus, it cannot be spread between people unless an organ transplant is involved with the organ already containing the fungus [2]. One of the most obvious sign of this disease is erythema nodosum, a reddish rash that can appear on the upper body and/or legs [8]. Other symptoms include chest pain, cough, shortness of breath and fever. Some patients may develop community acquired pneumonia (CAP) as early as a week after exposure to the fungus. Coccidioidomycosis is still under investigation. In 2015, there were over 11,000 cases reported to the Center for Disease Control and Prevention. It’s important to monitor the symptoms and learn why ten percent of the people who have this disease develop long term complications in their lungs. This under-recognized disease should be researched more to fully understand why one percent of that group also has the disease spread to other parts of the body. Although there is medication to treat coccidioidomycosis, we should invest our time and efforts into creating a vaccine that prevents it. Fig 1. The fungus that causes the disease, Coccidioides [2]

__References: __ [ 1] Rozman, D.; Strömstedt, M.; Waterman, M. R., The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family. Arch Biochem Biophys 1996, 333 (2), 466-74. [2] Valley Fever (Coccidioidomycosis). Center for Disease Control and Prevention 2016. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/risk-prevention.html (accessed Feb. 3, 2017) [3] National Center for Biotechnology Information. PubChem Compound Database; CID=55283, https://pubchem.ncbi.nlm.nih.gov/compound/55283 (accessed Feb. 5, 2017). [4] National Center for Biotechnology Information. PubChem Compound Database; CID=3365, https://pubchem.ncbi.nlm.nih.gov/compound/3365 (accessed Feb. 5, 2017). [5] Ampel, N. M., THE TREATMENT OF COCCIDIOIDOMYCOSIS. Rev Inst Med Trop Sao Paulo 2015, 57 Suppl 19, 51-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711193/ [6] Galgiani, J. N.; Ampel, N. M.; Blair, J. E.; Catanzaro, A.; Geertsma, F.; Hoover, S. E.; Johnson, R. H.; Kusne, S.; Lisse, J.; MacDonald, J. D.; Meyerson, S. L.; Raksin, P. B.; Siever, J.; Stevens, D. A.; Sunenshine, R.; Theodore, N., Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis 2016, 63 (6), 717-22. [7] Lanosterol 14-alpha demethylase. UniProt 2017, 1. http://www.uniprot.org/uniprot/P10614 [8] Davis, C. P. Valley Fever (Coccidioidomycosis). MediciNet 2016, 1-7. http://www.medicinenet.com/valley_fever/page4.htm [9] Early Fluconazole Treatment for Coccidioidomycosis Pneumonia. U.S. National Institutes of Health 2017, 1. https://clinicaltrials.gov/ct2/show/NCT02663674 [10] Cytochrome P450 (CYP450) tests. Mayo Clinic 2015, 1-4. http://www.mayoclinic.org/tests-procedures/cyp450-test/basics/definition/PRC-20013543 [11] Cytochrome P450. U.S. National Institutes of Health 2017, 1. https://ghr.nlm.nih.gov/primer/genefamily/cytochromep450

__External links: __ [|__https://www.cdc.gov/fungal/diseases/coccidioidomycosis/risk-prevention.html__] [|__http://www.mayoclinic.org/tests-procedures/cyp450-test/basics/definition/PRC-20013543__] [|__https://ghr.nlm.nih.gov/primer/genefamily/cytochromep450__] [|__https://clinicaltrials.gov/ct2/show/NCT02663674__] [|__http://www.medicinenet.com/valley_fever/page4.htm__]

=Target Information: Lanosterol 14 alpha-demethylase = Fluconazole and itraconazole mainly target the enzyme lanosterol 14α-demethylase. Lanosterol 14α-demethylase is a cytochrome P450 enzyme.

Size: 60,720 Daltons Location: Usually on chromosomes 3, 7 and 13 [1]. Usually found in liver cells but can be found in others. Within the cell, they can be found in the endoplasmic reticulum and the mitochondria. Function in a normal cell: The key function of the cytochrome P450 enzymes is to synthesize steroids, lipids and vitamins in eukaryotic cells. It also inhibits cell membrane formation [11]. P450 enzymes are used to process drugs and medications [10].

Drug Information: Fluconazole, Itraconazole
 Fig 2. Fluconazole chemical structure. [4]
 * __Fluconazole (Antifungal) __**

Chemical Formula: C13H12F2N6O Molecular weight: 306.277 g/mol CAS Number: 86386-73-4 Delivery method: by mouth or intravenously Side effects: nausea, headache, rash, vomiting, abdominal pain, diarrhea, and dizziness Other names: Diflucan Maker or company: Pfizer Is it patented? Yes, since 1981 Clinical Trials Info: In Phase IV of its clinical trials with the treatment of community acquired pneumonia (CAP) from coccidioidomycosis [9]. Start date of investigation was January of 2016. Estimated completion date of study is January 15th of 2021 Alternatives to this drug: Itraconazole

__** Itraconazole (Antifungal) **__  Fig 3. Itraconazole chemical structure. [3]

Chemical Formula: C35H38Cl2N8O4 Molecular weight: 705.64 g/mol CAS Number: 84624-61-6 Delivery method: orally Side effects: Similar to fluconazole (nausea, diarrhea, vomiting, headache, a rash). Others specific for this drug include fever, edema, cough, chest pain, depression, anxiety, constipation, fatigue and a urinary tract infection Other names: Sporanox Maker or company: Janssen Pharmaceutica, a branch of Johnson and Johnson Is it patented? Yes Clinical Trials Info: In progress Alternatives to this drug: Fluconazole