World Journal of Pharmaceutical Research Nandi et al. World Journal of Pharmaceutical SJIF ImpactResearch Factor 8.084 Volume 9, Issue 6, 1265-1287. Review Article ISSN 2277– 7105 RNA GENOME OF EBOLA VIRION AND VACCINATION BY MONOCLONAL ANTIBODIES *Kushal Nandi and Dr. Dhrubo Jyoti Sen Department of Pharmaceutical Chemistry, School of Pharmacy, Techno India University, Salt Lake City, Sector-V, EM-4, Kolkata-700091, West Bengal, India. ABSTRACT Article Received on 06 April 2020, Ebola, also known as Ebola virus disease (EVD), is a viral Revised on 27 April 2020, haemorrhagic fever of human and other primates caused by Accepted on 18 May 2020 DOI: 10.20959/wjpr20206-17705 ebolaviruses. Signs and symptoms typically start between two days and three weeks after contracting the virus with a fever, sore throat, muscular pain, and headaches. Vomiting, diarrhoea and rash *Corresponding Author usually follow, along with decreased function of the liver and kidneys. Kushal Nandi Department of At this time, some people begin to bleed both internally and Pharmaceutical Chemistry, externally. The disease has a high risk of death, killing 25% to 90% of School of Pharmacy, those infected, with an average of about 50%. This is often due to low Techno India University, blood pressure from fluid loss, and typically follows six to 16 days Salt Lake City, Sector-V, after symptoms appear. The disease was first identified in 1976, in two EM-4, Kolkata-700091, West Bengal, India. simultaneous outbreaks: one in Nzara (a town in South Sudan) and the other in Yambuku (Democratic Republic of the Congo), a village near the Ebola River from which the disease takes its name. EVD outbreaks occur intermittently in tropical regions of sub-Saharan Africa. Between 1976 and 2013, the World Health Organization reports 24 outbreaks involving 2,387 cases with 1,590 deaths. The largest outbreak to date was the epidemic in West Africa, which occurred from December 2013 to January 2016, with 28,646 cases and 11,323 deaths. It was declared no longer an emergency on 29 March 2016. Other outbreaks in Africa began in the Democratic Republic of the Congo in May 2017, and 2018. In July 2019, the World Health Organization declared the Congo Ebola outbreak a world health emergency. KEYWORDS: Virion, Fruit bat, Nucleocapsid, Monoclonal antibodies. www.wjpr.net Vol 9, Issue 6, 2020. 1265 Nandi et al. World Journal of Pharmaceutical Research INTRODUCTION The virus spreads through direct contact with body fluids, such as blood from infected humans or other animals. Spread may also occur from contact with items recently contaminated with bodily fluids. Spread of the disease through the air between primates, including humans, has not been documented in either laboratory or natural conditions. Semen or breast milk of a person after recovery from EVD may carry the virus for several weeks to months. Fruit bats are believed to be the normal carrier in nature, able to spread the virus without being affected by it. Other diseases such as malaria, cholera, typhoid fever, meningitis and other viral haemorrhagic fevers may resemble EVD. Blood samples are tested for viral RNA, viral antibodies or for the virus itself to confirm the diagnosis. Figure 1: Nucleocapsid of Ebola virion. Control of outbreaks requires coordinated medical services and community engagement. This includes rapid detection, contact tracing of those who have been exposed, quick access to laboratory services, care for those infected, and proper disposals of the dead through cremation or burial. Samples of body fluids and tissues from people with the disease should be handled with special caution. Prevention includes limiting the spread of disease from infected animals to humans by handling potentially infected bushmeat only while wearing protective clothing, and by thoroughly cooking bushmeat before eating it. It also includes wearing proper protective clothing and washing hands when around a person with the disease. An Ebola vaccine was approved in the United States in December 2019. While there is no approved treatment for Ebola as of 2019, two treatments (REGN- EB3 and mAb114) are associated with improved outcomes. Supportive efforts also improve www.wjpr.net Vol 9, Issue 6, 2020. 1266 Nandi et al. World Journal of Pharmaceutical Research outcomes. This includes either oral rehydration therapy (drinking slightly sweetened and salty water) or giving intravenous fluids as well as treating symptoms. Molecular genomics: Phylogenetic tree comparing ebolaviruses and marburgviruses. Numbers indicate percent confidence of branches. EBOV carries a negative-sense RNA genome in virions that are cylindrical/tubular, and contain viral envelope, matrix, and nucleocapsid components. The overall cylinders are generally approximately 80 nm in diameter, and have a virally encoded glycoprotein (GP) projecting as 7–10 nm long spikes from its lipid bilayer surface. The cylinders are of variable length, typically 800 nm, but sometimes up to 1000 nm long. The outer viral envelope of the virion is derived by budding from domains of host cell membrane into which the GP spikes have been inserted during their biosynthesis. Individual GP molecules appear with spacings of about 10 nm. Viral proteins VP40 and VP24 are located between the envelope and the nucleocapsid, in the matrix space. At the center of the virion structure is the nucleocapsid, which is composed of a series of viral proteins attached to an 18–19 kb linear, negative-sense RNA without 3′- polyadenylation or 5′-capping; the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins; this helix has a diameter of 80 nm. Figure-2: Phylogenetic tree. www.wjpr.net Vol 9, Issue 6, 2020. 1267 Nandi et al. World Journal of Pharmaceutical Research The overall shape of the virions after purification and visualization (e.g., by ultracentrifugation and electron microscopy, respectively) varies considerably; simple cylinders are far less prevalent than structures showing reversed direction, branches, and loops (e.g., U-, shepherd's crook-, 9-, or eye bolt-shapes, or other or circular/coiled appearances), the origin of which may be in the laboratory techniques applied. The characteristic "threadlike" structure is, however, a more general morphologic characteristic of filoviruses (alongside their GP-decorated viral envelope, RNA nucleocapsid, etc.). Figure 3: Ebolaviruses and Marburgvirus with host [fruit bat]. Genus inclusion criteria: A virus of the family Filoviridae is a member of the genus Ebolavirus if its genome has several gene overlaps its fourth gene (GP) encodes four proteins (sGP, ssGP, Δ-peptide, and GP1,2) using cotranscriptional editing to express ssGP and GP1,2 and proteolytic cleavage to express sGP and Δ-peptide peak infectivity of its virions is associated with particles ≈805 nm in length its genome differs from that of Marburg virus by ≥50% and from that of Zaire ebolavirus by <50% at the nucleotide level its virions show almost no antigenic cross reactivity with Marburg virions.[1] www.wjpr.net Vol 9, Issue 6, 2020. 1268 Nandi et al. World Journal of Pharmaceutical Research Types: The genera Ebolavirus and Marburgvirus were originally classified as the species of the now-obsolete genus Filovirus. In March 1998, the Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the genus Filovirus to the family Filoviridae with two specific genera: Ebola-like viruses and Marburg-like viruses. This proposal was implemented in Washington, D.C., as of April 2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington, D.C., to change the "-like viruses" to "-virus" resulting in today's Ebolavirus and Marburgvirus. The five characterised species of the genus Ebolavirus are 1. Zaire ebolavirus (ZEBOV): Also known simply as the Zaire virus, ZEBOV has the highest case-fatality rate, up to 90% in some epidemics, with an average case fatality rate of approximately 83% over 27 years. There have been more outbreaks of Zaire ebolavirus than of any other species. The first outbreak took place on 26 August 1976 in Yambuku. Mabalo Lokela, a 44-year-old schoolteacher, became the first recorded case. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact. The virus is responsible for the 2014 West Africa Ebola virus outbreak, with the largest number of deaths to date. 2. Sudan ebolavirus (SUDV): Like ZEBOV, SUDV emerged in 1976; it was at first assumed to be identical with ZEBOV. SUDV is believed to have broken out first amongst cotton factory workers in Nzara, Sudan (now in South Sudan), in June 1976, with the first case reported as a worker exposed to a potential natural reservoir. Scientists tested local animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The lack of barrier nursing (or "bedside isolation") facilitated the spread of the disease. The average fatality rates for SUDV were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001. 3. Reston ebolavirus (RESTV): This virus was discovered during an outbreak of simian hemorrhagic fever virus (SHFV) in crab-eating macaques from Hazleton Laboratories (now Covance) in 1989. Since the initial outbreak in Reston, Virginia, it has since been found in nonhuman primates in Pennsylvania, Texas, and Siena, Italy. In each case, the affected animals had been imported from a facility in the Philippines, where the virus has also infected pigs. Despite its status as a Level-4 organism and its apparent pathogenicity in monkeys, RESTV did not cause disease in exposed human laboratory workers. www.wjpr.net Vol 9, Issue 6, 2020. 1269 Nandi et al. World Journal of Pharmaceutical Research 4. Taï Forest ebolavirus (TAFV): Formerly known as "Côte d'Ivoire ebolavirus", it was first discovered among chimpanzees from the Tai Forest in Côte d'Ivoire, Africa, in 1994.