EBOV+Sp14

Ebola Hemorrhagic Fever
 * DISEASE/DRUG OF INTEREST: **

Ebola hemorrhagic fever, alternatively known as Ebola fever, is a severe disease that is caused by the Ebola virus (EBOV). This disease is extremely fatal, with a lethality of approximately 90% in humans and non-human primates. [[|2]] The disease is caused by various strains of the Ebola virus, which is named after a river in the Dominican Republic of Congo where it was first found. [[|2]] There are five different strains of the Ebola virus, of which four have been found to cause disease in humans. The last of these five strains has been found to affect non-human primates. The most virulent of these strains is the Ebola-Zaire. [[|1]] This virus strain was first discovered in the Dominican Republic of Congo, which was previously known as Zaire. [[|2]] The remaining three viruses, which have caused disease in humans, are Ebola-Sudan, Ebola-Ivory Coast, and Ebola-Bundibugyo. [[|2]] The final strain is known as Ebola-Reston. [[|2]]
 * MOTIVATION AND BACKGROUND: **

While the exact origin and nature of the Ebola virus are unknown, researchers theorize that the virus is zoonotic, or animal born. [[|2]] The precise wild reservoir of the Ebola virus is also unknown; however, it is most commonly found in gorillas, chimpanzees, and occasionally in other species like fruit bats. [[|4]] The first recorded outbreak of the Ebola fever was in 1976 and has appeared sporadically since. [[|2]] All recent cases of the epidemic have been isolated within Central Africa; no native strains of this virus are known to exist in the Americas or Australia. [[|3]] //Figure 1: Map delineating the areas in which Ebola virus has been encountered (shown in shades of orange depending on number of cases), along with a dotted line delineating possible zones of viral strains. //

The recorded infections involving Ebola viruses are acute, but after a first patient is infected with the virus, there are multiple methods in which it can be spread to a greater population. [[|2]] Ebola fever can be spread by bodily secretions and blood. Historically, most secondary patients are friends or family members of the first case patient, since they are usually in close contact with the patient and help in dealing with primary symptoms that seem otherwise commonplace. Alternatively, needles and other objects that have come into contact with a patient’s bodily fluid can spread the disease. [[|2]] During Ebola outbreaks, transmission can occur in a health-care setting where many doctors may not use gloves or other protective gear. Recent outbreaks in the past decade have spurred many health care professionals in Ebola-prone areas to adopt more rigorous safety measures for both themselves, and the patients. [[|5]] No specific population is more susceptible to the disease; however, as is the case with many infectious diseases, survivors are usually young, fit individuals whose immune systems are better equipped to deal with complications. [[|2]]

Initial symptoms of Ebola fever, which occur during the incubation period of one or two weeks, include arthritis, chills, diarrhea, headache, fever, vomiting, and body aches. Later symptoms include uncontrolled bleeding from orifices such as the eyes, nose, mouth, and rectum. The hallmark of Ebola fever is the hemorrhagic rash. [[|2]] No known cure for the Ebola virus exists, and antivirals made for other diseases are ineffective. [[|5]] The only treatment for the disease is supportive, and usually involves replenishing electrolytes, blood, and blood plasma, as well as maintaining blood pressure and treating minor infections.

Despite the rare occurrence of the Ebola fever, many researchers are dedicated to find a cure for the disease. Hemorrhagic fever viruses have been used by the Soviet Union, Russia, and the United States as weapons. [[|1]] Up until 1992, Russia and the Soviet Union produced sizeable quantities of both Marburg and Ebola viruses, which stem from the same family. [[|4]] Various studies have also proven the efficacy of aerosol preparations of these viruses in widespread infection. [[|4]] These finding demonstrate that Ebola could be used as a biological weapon in the future, and has since been designated a category A bioweapon by the Centers for Disease Control and Prevention. [[|2]] For this reason, researchers have been working on finding an inhibitor that could possibly disable the glycoprotein, which causes the symptoms of Ebola fever. Many compounds have been tested, but there have yet to be neither conclusive findings nor positive clinical trials.

//Figure 2: Illustration showing the Ebola virus-encoded proteins (pink) embedded in the host cell's lipid bilayer (gray). // http://animations.3d4medical.com/The-life-cycle-of-the-Ebola-virus-Part-1-of-2-animation_AN2058.html http://animations.3d4medical.com/The-life-cycle-of-the-Ebola-virus-Part-2-of-2-animation_AN2337.html
 * EBOLA LIFE CYCLE ANIMATION: **


 * TARGET INFORMATION: **

 The glycoprotein of Ebola has two separate subunits termed GP1 and GP2, which have distinctive structural and functional roles. [[|3]] While GP1 is responsible for reception, GP2 is responsible for viral and host membrane fusion. [[|3]] These two structures form the most accurate representation of the Ebola virus, which is a three-lobed protein structure, resembling a goblet, which weighs 450 kDa. [[|3]] The deeper portion is formed by the subunits of GP1, while the stem is formed by three subunits of GP2. Although hydrophobic residues cover the GP1 subunits, the GP2 subunits are susceptible to fusion of host and viral membranes. Figure 3, which is a diagram of the virus, is novel. It identifies the probable cleavage site of the glycoproteins which was previously unknown. [[|3]] It provides an indispensible illustration of the mechanism of the cleavage and interaction between host receptors. [[|3]] This is important as it shows that a dense layer of carbohydrate covers a majority of the glycoprotein, leaving minimal sites exposed for antibody binding. This structure currently serves as a template for vaccines and antibodies directed at targeting these novel sites of inhibition. [[|3]] //Figure 3: Side and bottom view of the crystal structure of the Ebolavirus GP with GP1 and GP2 subunits labeled. //
 * <span style="font-family: Georgia,serif; font-size: 110%;">DRUG INFORMATION: **

<span style="font-family: Georgia,serif; font-size: 110%;"> No drugs have been identified for the treatment of the Ebola virus. Although some have been correlated with efficacy in primates, the results were not substantial enough to test on human subjects successfully. No clinical trials have provided conclusive results to date.


 * <span style="font-family: Georgia,serif; font-size: 110%;">REFERENCES: **
 * 1) <span style="font-family: Georgia,serif; font-size: 110%;">Borio, L.; Inglesby, T.; Peters, C. J.; Schmaljohn, A. L.; Hughes, J. M.; Jahrling, P. B.; Ksiazek, T.; Johnson, K. M.; Meyerhoff, A.; O'Toole, T.; Ascher, M. S.; Bartlett, J.; Breman, J. G.; Eitzen, E. M.; Hamburg, M.; Hauer, J.; Henderson, A.; Johnson, R. T.; Kwik, G.; Layton, M.; Lillibridge, S.; Nabel, G. J.; Osterholm, M. T.; Perl, T. M.; Russell, P.; Tonat, K.; Working Grp Civilian, B., Hemorrhagic fever viruses as biological weapons - Medical and public health management. Jama-Journal of the American Medical Association 2002, 287 (18), 2391-2405.
 * 2) <span style="font-family: Georgia,serif; font-size: 110%;">[]
 * 3) <span style="font-family: Georgia,serif; font-size: 110%;">Lee, J.E.; Fusco, M.L.; Oswald, W.B.; Hessell, A.J.; Burton, D.R.; Saphire, E.O., Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 2008, 454 (7201),177-182.
 * 4) <span style="font-family: Georgia,serif; font-size: 110%;">Leroy, E. M.; Kumulungui, B.; Pourrut, X.; Rouquet, P.; Hassanin, A.; Yaba, P.; Delicat, A.; Paweska, J. T.; Gonzalez, J. P.; Swanepoel, R., Fruit bats as reservoirs of Ebola virus. Nature 2005, 438 (7068), 575-576.
 * 5) <span style="font-family: Georgia,serif; font-size: 110%;">Sullivan, N. J.; Sanchez, A.; Rollin, P. E.; Yang, Z. Y.; Nabel, G. J., Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000, 408 (6812), 605-609.
 * 6) <span style="font-family: Georgia,serif; font-size: 110%;">http://visualscience.ru/en/projects/ebola/illustration/