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Emerging Therapeutic Approaches to Combat the Pandemicity of The Review Article Emerging Therapeutic Approaches to Combat the Pandemicity of the Deadly Ebola Virus Minyahil Alebachew Woldu*1, Jimma Likisa Lenjisa2, Gobezie Temesgen Tegegne2 and Gizaw Dabessa Satessa2 1Department of pharmacology and clinical pharmacy, School of pharmacy, college of health sciences, Addis Ababa University, Addis Ababa-Ethiopia 2Clinical pharmacy unit, department of pharmacy, college of medicine and health sciences, Ambo University, Ambo-Ethiopia ABSTRACT Background: Since the identification of Ebola Virus (EBOV) in 1976, significant filovirus research has focused on developing antiviral therapies. However, despite promising vaccine candidates, no licensed prophylactics currently exist for preventing or treating filovirus infections. Pathogenesis: The Ebola genome encodes only seven genes, which mediate the entry, replication, and egress of the virus from the host cell. Bats have been identified as a reservoir for Ebola viruses but it remains unclear if transmission to an end host involves intermediate hosts. Diagnosis: Diagnosis within a few days after symptoms begin involves antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, polymerase chain reaction (PCR) and Virus isolation. Clinical pictures: Initial signs and symptoms are nonspecific and may include fever, chills, myalgias, and malaise. Sufferers Address for experience nausea, vomiting, internal bleeding and organ failure Correspondence before they die. Treatment: There are no approved treatments or vaccines available Department of for Ebola virus disease (EVD) until today; however, there are a pharmacology and bunch of therapeutic approaches on the track which could have the clinical pharmacy, School of pharmacy, real impact on control and prevention of this global threat. Among college of health these, the one announced by the WHO opens some ones eyebrow and sciences, Addis Ababa gives the real glimmer of hope to tackle EVD. The two “front University, Addis running” vaccines on the track are cAd3-ZEBOV, a chimpanzee Ababa-Ethiopia. derived adenovirus vaccine developed by GlaxoSmithKline in E-mail: conjunction with the US National Institute of Allergies and Infectious [email protected] Diseases, and rVSV-ZEBOV, developed by the Public Health Agency of Canada and now licensed to a US company called New American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Woldu et al_________________________________________________ ISSN 2321 – 2748 Link. Conclusions: Many promising vaccines are moving through pre- clinical or clinical trials, but mass immunization is unlikely due to the localized and sporadic nature of EBOV infections. Post- exposure interventions are therefore necessary for the treatment of cases as they occur. Keywords: EBOV, Ebola virus, EHF, Ebola hemorrhagic fever, Filoviridae, Filovirus. BACKGROUND An Ebola Hemorrhagic Fever (EHF) currently exist for preventing or treating is zoonotic pathogen caused by the filovirus infections9. Filoviridae family, Ebolavirus (EBOV)1,2. Two genera compose the family Filoviridae: Case definition for Ebola virus disease Ebolavirus and Marburgvirus3. There are (EVD) five antigenically distinct species of Ebola viruses: Zaire ebolavirus (EBOV), Sudan Person under investigation (PUI) A person who has both consistent ebolavirus (SUDV), Bundibugyo ebolavirus 10 (BDBV), Tai Forest ebolavirus (TAFV), symptoms and risk factors as follows : and Reston ebolavirus (RESTV) (4). All of Clinical criteria, which includes fever of these viruses cause disease in humans except greater than 38.6 degrees Celsius or 101.5 RESTV, which is pathogenic in nonhuman degrees Fahrenheit, and additional primates3 (Figure 1). symptoms such as severe headache, EBOV has been endemic to sub- muscle pain, vomiting, diarrhea, Saharan Africa and has high mortality rates in abdominal pain, or unexplained humans1,2. Currently it represents a significant hemorrhage; AND challenge to global public health, causing a 1. Epidemiologic risk factors within the past severe hemorrhagic fever with case fatality 21 days before the onset of symptoms, rates of up to 90%5,6. such as contact with blood or other body Filovirus outbreak is one of the most fluids or human remains of a patient fatal viral diseases worldwide affecting known to have or suspected to have EVD; humans and nonhuman primates (NHPs)7 and residence in or travel to an area where therefore, EBOV is identified as a biosafety EVD transmission is active; or direct level 4 pathogens and CDC category A agents handling of bats or non-human primates of bioterrorism6. Furthermore, the lack of from disease-endemic areas. preventive vaccines and FDA- approved therapeutics has struck fear that the Probable case EBOV could become a pandemic threat8. A PUI whose epidemiologic risk Since the identification of EBOV in factors include high or low risk exposure 10 1976, significant filovirus research has (s) . focused on developing antiviral therapies. However, despite promising vaccine Confirmed case candidates, no licensed prophylactics A case with laboratory-confirmed diagnostic evidence of Ebola virus infection10. AJPCT[2][11][2014]1287-1298 Woldu et al_________________________________________________ ISSN 2321 – 2748 Pathogenesis Once infected, humans transmit the disease through body fluids, including breast The Ebola genome milk. Funerals, which can bring dozens of The Ebola genome encodes only people in contact with the remains of Ebola seven genes, which mediate the entry, patients, are particularly dangerous and replication, and egress of the virus from the 8 gatherings for suspected victims of the virus host cell . EBOV entry requires the virion have also been outlawed12. It is also being surface-associated glycoprotein (GP) that is afraid that EBOV can become airborne13. composed of a trimer of heterodimers EBOV entry is rapid, with viral (GP1/GP2). The GP1 subunit contains two protein expression detectable within 2 h after heavily glycosylated domains, the glycan cap infection5. After the initial transmission, the and the mucin-like domain (MLD). The viruses can spread from person to person glycan cap contains only N-linked glycans, through contact with body fluids or whereas the MLD contains both N- and O- 14 3 contaminated needles . linked glycans (Figure 2). The genomes of filoviruses (Marburg The virulence nature of Ebola virus (MARV) and EBOV) are ∼19 kb, single Ebola virus enters the patient through stranded, negative sense RNA molecules mucous membranes, breaks in the skin, or encoding a total of 7 genes (NP, VP35, VP40, parenterally and infects many cell types, GP, VP30, VP24, L) separated by intergenic including monocytes, macrophages, dendritic regions of varying lengths and flanked by cells, endothelial cells, fibroblasts, untranslated regions (UTRs) at the 3′ and 5′ 9 hepatocytes, adrenal cortical cells and ends . epithelial cells. The incubation period may be Viral protein 35 (VP35), encoded by related to the infection route (e.g., 6 days for filoviruses, is a multifunctional dsRNA injection versus 10 days for contact)15. binding protein that plays important roles in The virulence of EBOV can be viral replication, innate immune evasion, and attributed to several immunoevasion pathogenesis. The multifunctional nature of mechanisms: an early inhibition of innate these proteins also presents opportunities to immunity started by the down regulation of develop countermeasures that target distinct 11 type I interferon, epitope masking and functional regions . The EBOV matrix subversion of the adaptive humoural protein is VP40, which is also found localized immunity by secreting a truncated form of the under the lipid envelope of the virus where it viral glycoprotein16. bridges the viral lipid envelope and nucleocapsid. The VP40 is effectively a Diagnosis peripheral protein that mediates the plasma The currently available screening membrane binding and budding of the virus 8 technique include wild-type or recombinant prior to egress (Figure 2&3). viruses13. Diagnosing Ebola in an person who has been infected for only a few days is Mode of transmission difficult, because the early symptoms, such as Bats have been identified as a fever, are nonspecific to Ebola infection and reservoir for Ebola viruses but it remains are seen often in patients with more unclear if transmission to an end host involves commonly occurring diseases, such as intermediate hosts. In 2013, one of the malaria and typhoid fever10. (See table 1.) Ebola species was found in Philippine pigs Platelet counts are often decreased in raising concerns regarding animal health and the 50,000 to 100,000 range. Amylase may be food safety2. AJPCT[2][11][2014]1287-1298 Woldu et al_________________________________________________ ISSN 2321 – 2748 elevated, reflecting pancreatic involvement Treatment (inflammation/infection). Hepatic transami- nases are elevated with aspartate Current treatment approaches aminotransferase (AST) exceeding alanine There are no approved treatments aminotransferase (ALT); these values may available for EVD. Clinical management peak at more than 1,000 IU/L. Proteinuria should focus on supportive care of may be present. Prothrombin (PT) and partial complications, such as hypovolemia, thromboplastin times (PTT) are prolonged electrolyte abnormalities, hematologic and fibrin degradation products are elevated, abnormalities, refractory shock, hypoxia, consistent with disseminated intravascular hemorrhage, septic shock, multi-organ failure, 15 and DIC15. There is
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