Gonorrhea.

=__**Disease/Drug of interest** : __= __ Gonorrhea __

**Motivation and Background** :
Gonorrhea, Neisseria gonorrhoeae, or known as “the clap”, is a sexually transmitted disease that is not bias to gender or age. It is found most in young adults and adolescents between the ages 15-24. Gonorrhea is a negative pathogen that binds to and infects mucosal surfaces. The sexually transmitted disease is found in the urethritis in men and endocervicitis in women. Gonorrhea is treatable, but just like other diseases, Gonorrhea is developing resistance to treatment. Most people do not know they have it and can become dangerous to one’s health if it goes untreated. Pregnant women without treatment can spread gonorrhea to their offspring, usually blinding the child. If untreated, gonorrhea can lead to serious long-term health problems such as endometritis, pelvic inflammatory disease, ectopic pregnancy, epididymitis, and infertility. Symptoms of gonorrhea include burning sensation when urinating, discharge, and painful or swollen testicles in males or vaginal bleeding between periods in females. Anyone who is sexually active is at risk of getting Gonorrhea. It is transmitted through oral, anal, and vaginal sex. Many young adults are unaware and uneducated about the severity of sexually transmitted diseases. It is important to take precaution and use protection to prevent any spread of diseases. Gonorrhea can be treated through antibiotics. If someone is diagnosed with Gonorrhea they often have Chlamydia as well. Gonorrhea requires dual therapy through Ceftriaxone and Azithromycin.

Figure 1: Gonorrhea


 * References: **

1. Hooda, Y.; Lai, C. C.; Judd, A.; Buckwalter, C. M.; Shin, H. E.; GrayOwen, S. D.; Moraes, T. F., Slam is an outer membrane protein that is required for the surface display of lipidated virulence factors in Neisseria. Nat Microbiol 2016, 1, 16009. 2. Roberts, S. B.; Spencer-Smith, R.; Shah, M.; Nebel, J. C.; Cook, R. T.; Snyder, L. A., Correia Repeat Enclosed Elements and NonCodingRNAsintheNeisseria Species. Microorganisms 2016, 4 (3). 3. Tomberg, J.; Fedarovich, A.; Vincent, L. R.; Jerse, A. E.; Unemo, M.; Davies, C.; Nicholas, R. A., Alanine-501 Mutations in PenicillinBinding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness. Biochemistry 2017. 4. Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, ChangZ, Woolsey J. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D668-72. 16381955

**External links:**
Binding of Ceftriaxone: https://www.ncbi.nlm.nih.gov/pubmed/3424863 Clinical Trials: https://clinicaltrials.gov/ct2/show/NCT02196493 Azithromycin Origin: http://www.wipo.int/ipadvantage/en/details.jsp?id=906

=__**Target Information** : __= Ceftriaxone binds to and inactivates penicillin-binding proteins(PBP) that are located on the inner membrane of the bacterial cell wall. Ceftriaxone also binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. By binding to these enzymes, ceftriaxone results in the formation of defective cell walls and cell death. Ceftriaxone has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. Azithromycin is the second antibiotic that is used to treat gonorrhea. Azithromycin inhibits protein synthesis and binds reversibly to 50S ribosomal subunits.

** Size ** :
The molecular weight of carboxypeptides-transpeptidase is 38,000 g/mol, the endopeptidase estimated molecular weight is 80,000 g/mol.

** Location ** :
Carboxypeptidases is an enzyme that is synthesized in the pancreas and secreted into the small intestine.

** Function in a normal cell ** :
The three enzymes carboxypeptidases, endopeptidases, and transpeptidases are involved in cell wall synthesis and division.

=__**Drug Information**** : **__=


 * Schematic figure of drug ** :

Figure 2: Structural figure of Ceftriaxone

Figure 3: Azithromycin binds reversibly to 50s ribosomal subunit

Figure 4: Structural figure of Azithromycin, a methyl-substituted nitrogen atom is incorporated into the lactone ring.

Ceftriaxone: C18H18N8O7S3 Azithromycin: C38H72N2O12
 * Formula ** :

Ceftriaxone: 554.58 g/mol Azithromycin: 748.9845 g/mol
 * Molecular weight ** :

Ceftriaxone: 73384-59-5 Azithromycin: 83905-01-5
 * CAS Number ** :

Ceftriaxone is given through injection. Azithromycin is prescribed as a tablet.
 * Delivery method ** :

Ceftriaxone may cause a hard lump where the injection is given, nausea, vomiting, headache, swelling in the tongue, sweating or vaginal itching or discharge.Side effects of azithromycin include diarrhea, vomiting, stomach pain, dizziness, nervous feeling, vaginal itching, rash, and ringing in ears.[2]
 * Side effects ** :

Ceftriaxone is sold as Rocephin. Azithromycin is sold as Zithromax or Sumamed.
 * Other names ** :

Roche Diagnostics Corp. is the company of Ceftriaxone. Pfizer is the maker of Azithromycin.
 * Maker or company ** :

Ceftriaxone is not patented, but Azithromycin is patented by Pliva and later was branded by Pfizer.
 * Is it patented ** ?

Ceftriaxone clinical trials have been complete. Azithromycin is currently in the process of recruiting participants for clinical trials.
 * Clinical Trials Info ** :

__** Origin ** : __ Ceftriaxone was discovered by Hoffmann-LaRoche and originated in Turkey. Azithromycin was first made in 1980 and is derived from erythromycin by adding a nitrogen atom into the lactone ring of erythromycin.

Zithromax - Pfizer's branded version of Azithromycin - was one of the best selling branded antibiotics in the United States and worldwide, with total sales peaking at US$ 2 billion in 2005 before starting to decline with the loss of patent protection in 2006 and resulting generics competition.
 * Miscellaneous ** :

Ceftriaxone can be used to treat a wide variety of bacterial infections but not viruses.
 * Other uses ** :