Sandbox Reserved 1687

Disease

A specific DNA complex of the 65-residue, N-terminal fragment of the yeast transcriptional activator, GAL4, has been analysed at 2.7 A resolution by X-ray crystallography. The protein binds as a dimer to a symmetrical 17-base-pair sequence. A small, Zn(2+)-containing domain recognizes a conserved CCG triplet at each end of the site through direct contacts with the major groove. A short coiled-coil dimerization element imposes 2-fold symmetry. A segment of extended polypeptide chain links the metal-binding module to the dimerization element and specifies the length of the site. The relatively open structure of the complex would allow another protein to bind coordinately with GAL4.

EVD pathogenesis in humans consists of three phases with symptoms normally occurring after an incubation period of 2-21 says (Furuyama & Marzi, 2019). In the first phase, symptoms during the first few days include nonspecific fever, headache, and myalgia (Furuyama & Marzi, 2019). This is followed by a “gastrointestinal phase” characterized by symptoms including diarrhea, vomiting, abdominal discomfort, and dehydration (Furuyama & Marzi, 2019). The final and advanced phase of the illness consist of kidney and liver function failure, often resulting in “metabolic compromise, convulsion, shock, and death due to mucosal bleeding, bloody diarrhea, and multi-organ failure within 16 days after the first symptoms appear” (Furuyama & Marzi, 2019).

The most recent outbreak of Ebola occurred during a three-month span in the Democratic Republic of the Congo this year, the country’s 4th in the past three years (Thomas, 2021). Since its start in February, there was a total of eleven confirmed cases with six recoveries and six deaths and one probable case emanating from four health zones in North Kivu (Thomas, 2021). There is also an ongoing outbreak in Guinea, West Africa which started in the same month as the outbreak in the DRC (Thomas, 2021).

There are currently eight vaccine candidates in human clinical trials that all target the Ebola virus glycoprotein (GP), one of the nine known proteins to be expressed by the virus’s genome (Furuyama & Marzi, 2019). However, these vaccines are different from each other in the “immune responses they elicit, the antigen delivery system, and the side-effect profile" (Furuyama & Marzi, 2019).

RNA Classification

Ebola is part of the Filoviridae family of single-stranded negative-sense RNA viruses of approximately 19 kb (Furuyama & Marzi, 2019). The 19 kb RNA encodes for “glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30, 40) and the RNA dependent RNA polymerase” (Rojas et al., 2020).

Function of RNA-Dependent RNA Polymerase

Structural Features of Ebola Virus RNA-Dependent RNA Polymerase