Supercomputer simulations target the deadly coils of Ebola.


Stampede2, Bridge simulations demonstrate vulnerabilities in nucleocapsid viruses.

It is difficult to estimate how lucky people outside of Africa were to survive the deadly Ebola virus outbreak in the midst of the global COVID-19 pandemic.

It incapacitates its patients with massive vomiting or diarrhea soon after infection and induces death from fluid loss in around 50 percent of those who contract the illness.

The Ebola virus is transmitted by body fluids alone, which is a crucial distinction from the COVID-19 virus and has helped to control the spread of Ebola.

Ebola outbreaks continue to occur in West Africa, although Ebola has been kept at bay by a vaccine established in December 2019 and progress in treatment and containment. Supercomputer simulations by a team from the University of Delaware, which included a student funded by the XSEDE EMPOWER program, are helping to crack the convoluted genetic makeup defenses of Ebola.

This new research could lead to breakthroughs in the treatment of Ebola and other deadly viral diseases such as COVID-19, as well as improved vaccines.

“Our major findings relate to the stability of the Ebola nucleocapsid,” said Juan R. Perilla, an assistant professor at the University of Delaware’s Department of Chemistry and Biochemistry. Perilla co-authored a report published in the Chemistry Physics AIP Journal in October 2020.

It concentrated on the nucleocapside, a protein coat that protects the genetic material used by Ebola to reproduce from the defenses of the body.

“What we found is that the Ebola virus has evolved to regulate the stability of the nucleocapsid by forming electrostatic interactions with its RNA, its genetic material,” Perilla said. “There is an interplay between the RNA and the nucleocapsid that holds it together.”

The Ebola virus depends on a rod-shaped and helical nucleocapsid to complete its life cycle, like coronaviruses.

Specifically, in a helical configuration, structural proteins called nucleoproteins assemble to encapsulate the nucleocapsid-forming single-stranded viral RNA genome (ssRNA).

Preparation of nucleocapsid Ebola virus systems for simulations of atomistic molecular dynamics.

Three nucleoprotein structural domains were found in the viral monomer: the N-terminal arm (yellow), the N-terminal lobe (brown), and the C-terminal lobe (dark green), as well as the bound RNA segment (red).

Credit: Juan R. Perilla, Delaware University.
The research by Perilla and his team of scientists searched for the molecular determinants of nucleocapsid stability, such as how the ssRNA genome is packaged, the system’s electrostatic potential, and the helical assembly residue structure.

To develop new therapeutics against Ebola, this information is necessary. Yet for even the best experimental laboratories in the world, this information remains out of control.

This void can and has, however, been filled by computer simulations.

“You can think of the simulation work as a theoretical extension of the experimental work,” says Tanya Nesterova, co-author of the research, a graduate student at the Perilla Lab. “We found that RNA is strongly negatively charged and helps stabilize the nucleocapsid through electrostatic interaction with the mostly positively charged nucleoproteins,” she said.

Through a 2019 XSEDE Expert Mentoring Generating Opportunities for Work, Education, and Study (EMPOWER) grant, which promotes undergraduate engagement in XSEDE’s real work, Nesterova received funding.

She said, “It was an effective program,” “This summer we used machine tools like Bridges.

In order to keep our development up to date, we also had daily contact with the coordinator.

Ebola virus nucleocapsid molecular surface representation with bound RNA.

Credit: Juan R. Perilla, Delaware University.
The team created an Ebola nucleocapsid molecular dynamics simulation, a device comprising 4.8 million atoms.

They used the Ebola virus’ cryo-electron microscopy structure, published in Nature in October 2018, as data to create the model.

“We built two systems,” said study co-author Chaoyi Xu, a Perilla Lab graduate student. One device is the RNA nucleocapside of Ebola.

And as a power, the other is just the nucleocapsid.

We placed each nucleocapsid in an environment similar to the cell after we built the whole tube,”After we built the whole tube, we put each nucleocapsid in an environment similar to the cell,”

Basically, they added ions of sodium chloride and inserted d


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