Bowdoin Science Journal

Matt Lallier

Groundbreaking Ebola Virus Disease Treatment In Development to Reduce Infections and Case Fatality

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Introduction

The Ebola virus disease (EVD) was discovered in Africa in 1976. It causes excessive bleeding in humans and some primates and is often fatal. EVD is highly transmissible and is spread by direct contact (Jacob et al., 2020). There are six known strains of EVD today: Zaire, Sudan, Tai Forest, Bundibugyo, Reston, and Bombali. All except the Reston and Bombali strains can cause diseases in humans. Its transmission into humans is believed to have occurred when Patient Zero went hunting and consumed the meat of an infected animal (Jacob et al., 2020). In the years since its discovery, there have been dozens of outbreaks worldwide, mostly in Africa and Europe (Mohd et al., 2024).

The Sudan strain of EVD has nearly a 90% case-fatality rate, and the disease is usually fatal within a month. This virus appears and disappears in sporadic epidemics, which makes it difficult to find cures for. Viruses are more difficult to preserve in a lab than bacterial or fungal samples since viruses require host cells to stay alive, and since EVD is caused by a virus rather than a bacteria, it is difficult to keep samples intact in a laboratory for ongoing studies after an outbreak ends. Survivors of EVD generate antibodies to the virus, which serves as an EVD-specific line of defense should they be infected again (Jacob et al., 2020). The search for a cure to EVD has centered around the production of such antibodies without exposing patients to the disease first.

Vaccines are created by introducing weakened or inactive forms of a virus to the body. This agent does not have the capacity to cause disease in the patient. However, it demonstrates for the immune system what the active form of that virus would look like and allows the body to create antibodies to prepare for a full infection, should one ever occur. The immune system uses this experience to prepare for an infection by generating antibodies specific to the pathogen introduced. Monoclonal antibodies (immune signaling chemicals that alert B and T cells of the presence of specific pathogens) can also be artificially created and introduced directly into the body, which is another type of treatment made possible by this study.

EVD infects hosts when individual virus particles bind to healthy body cells and hijack the cell’s machinery to create more viruses. All cells have receptor sites on their membranes that are used for communication. Each receptor type is unique and fits the shape of a specific messenger chemical (ligand) which is absorbed into the cell for processing. Some ligands, however, are structurally similar enough to pathogen surface proteins that their respective receptors can be used to absorb pathogens into a cell. The cell has no way of knowing what is attached to the molecule binding to it, so a pathogen can easily enter a cell this way (Hastie et al., 2025).

EVD’s RNA genome codes for seven proteins, five of which contribute to the external structure of virus particles. One such structural protein is the glycoprotein (a molecular signal composed of protein-like and sugar-like parts) on the surface of Ebola particles, which is essential for the pathogen to bind to and enter host cells.

Methods

Glycoproteins, which are sometimes called spike proteins, are diverse among pathogens and therefore are an effective segment to use to create an array of effective vaccines. In this experiment, researchers at the La Jolla Institute for Immunology used x-ray crystallography to visualize the structure of an Ebola particle. The surface glycoproteins 1 and 2 were isolated from the Ebola virus to investigate the sites where the virus is able to bind to human cells (Hastie et al., 2025).

Results

This experiment revealed through in vitro and mouse trials that a receptor known as 3A6 on human cell membranes is the binding site for EVD through both glycoproteins 1 and 2 (Hastie et al., 2025). Since site 3A6 binds to these unique proteins, monoclonal antibodies that would target EVD pathogens would have a similar structure. Once such antibodies can be created, the body has a method for detecting EVD particles in the bloodstream and destroying them before they can replicate beyond control.

Conclusion and Discussion

Now that the method of cell entry for Ebola virions has been studied, the next step is to create accessible treatments – both preventative and therapeutic – for people at risk of contracting EVD. It is known that the glycoproteins 1 and 2 studied here have a relatively slow rate of mutation on a viral scale, which means that any treatments that can be manufactured to focus on these spike proteins will be effective for a long time. In other words, a person who has been exposed to a vaccine containing an inactive Ebolavirus glycoprotein 1 or 2 will have a better outcome if infected than they would if they had been vaccinated with a different piece of the virus. On the other hand, flu vaccines need to be renewed every year because influenza spike proteins mutate much faster, which means that immunity to the spike protein of last year’s strain becomes obsolete as soon as a new strain takes hold.

Knowledge of the 3A6 binding site is valuable for eventual immunity to EVD and related filoviruses. As with any disease, when more people become vaccinated against it, it becomes less likely that deadly outbreaks will continue appearing as sporadically as they do.

Works Cited:

Hastie, Kathryn M., et al. “Anti-Ebola Virus MAb 3A6 Protects Highly Viremic Animals from Fatal Outcome via Binding GP(1,2) in a Position Elevated from the Virion Membrane.” Nature Communications, vol. 16, no. 1, Nature Portfolio, Feb. 2025, https://doi.org/10.1038/s41467-025-56452-2. Accessed 7 Feb. 2025..

Jacob, Shevin T., et al. “Ebola Virus Disease.” Nature Reviews Disease Primers, vol. 6, no. 1, Feb. 2020, www.nature.com/articles/s41572-020-0154-4..

Mohd, Omar B., et al. “The Development of Ebola Virus Outbreaks: A Review of Epidemiological Trends, Clinical Features, and Treatment Advances.” Cureus, Cureus, Inc., Nov. 2024, https://doi.org/10.7759/cureus.74078. Accessed 11 Jan. 2025..

Better Bonds and New Molecules

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Keywords – chemical bonds, covalent bonds, ionic bonds, ions, free radicals, dissociation, synthesis, stimuli, heterolysis

Free radicals are typically atoms that are most commonly found in diatomic molecules (for example, Oxygen) that are not bonded, so they tend to bond to the first available molecule and are therefore very unpredictable. Free radicals are atoms with unpaired electrons attached. They are commonly found in the body or in the environment. Having unpaired electrons means that they are volatile and can randomly bond to other molecules, creating toxic compounds if they become too abundant. 

By contrast, ions are atoms with charges that create much more predictable bonds in nature. Like free radicals, ions have a different number of electrons (negatively charged parts) than protons (positively charged parts). However, ions have paired electrons and occur more naturally in the body. Ions are essential for communication between cells.

The synthetic breakdown – or dissociation – of molecules in solutions or bodily environments often releases free radicals instead of ions. This new study explores the possibility of using energy differently to reduce the release of free radicals in synthetic dissociation. The replacement of free radicals with ions will reduce harm to the body, as well as the environment. This opens up new possibilities for the creation of new medicines and more efficient biofuels.

Heterolysis results in the release of ions rather than free radicals. The Nuerberger and Breder lab conducted experiments that center around the understanding that many molecules can not be dissociated into their respective atomic contents via heterolysis, a process that involves breaking molecular bonds by using two different energetic stimuli rather than one (for example, light and heat rather than one or the other). The challenge here is to balance the use of heat and light to efficiently break down molecules without harmful byproducts like free radicals.

This procedure begins with determining the lambda-max value, which is the optimal wavelength of light that will maximize the absorbance in a certain molecule, for the molecules PhSe, PhSe+, and PhSe- (Breder, 2024). These are charged compounds consisting of a Selenium atom attached to a phenyl group, or a six-Carbon ring with five attached Hydrogen atoms. These molecules were selected to mimic the complexity and size of many biological molecules found in the body.

Next, the researchers determined the amount of energy that could be absorbed from a light source with the calculated lambda-max wavelength. This data was obtained through the use of absorbance sensors, which shine a broad spectrum of light with various wavelengths and can detect which wavelengths are blocked the most by dissolved particles. All substances have a lambda-max value, which is why we are able to see in color. Even samples that appear to be colorless have a slight color to them. The lambda-max value of a sample will typically correspond to its complementary color in the red-blue-green system (for example, the lambda-max value for a green substance will correspond to a shade of purple light).

Once the lambda-max values were determined for each substance, the researchers calculated how much energy was contained in the absorbed light. This value was subtracted from the known amount of energy required to break the Se-C (Selenium-Carbon) bonds. The remaining energy was supplemented in the form of heat, and the molecules in turn dissociated with a much higher frequency of ions and atoms with paired electrons than free radicals (Breder, 2024). Researchers were able to quantify the difference in ion dissociation from free radicals by determining experimental lambda-max values after exposure to the light and heat stimuli and comparing those of the ion products and of the free radical products. (see Figure 1 for comparison)

Figure 1. Comparison of average energy levels required to separate atoms via homolysis vs. heterolysis (Breder, 2024). 

 

This experiment demonstrates that the combined use of heat and light stimuli to dissociate molecules results in safer byproducts for the human body and the environment. This means that more diverse molecules can be created without extensive energy usage. This leap in chemistry expands into the biological and environmental fields of research, allowing for more complex and efficient medicines, implants, biofuels, plastic replacements, and more to be created.

This research has broad implications in the research world. In environmental sciences, the creation of biofuels can require several steps of synthesizing and dissociating molecules to achieve specific formulas and structures. The knowledge of how to minimize the release of volatile materials during this process is vital to ensuring that living organisms in nearby ecosystems are not harmed by the creation of more renewable fuels.

In medicine, a similar dilemma occurs with the creation of new drugs. While medicinal compounds are synthesized in controlled lab environments, their individual chemical formulas may be counterproductive in that they favor the release of free radicals in the body once administered into such an uncontrolled environment. In addition to reducing the abundance of free radicals in the synthesis of new materials, the knowledge of how to more efficiently construct and break apart molecules opens up new possibilities for entirely unique drug compounds. Ideally, many of these will serve the same functions but will be less structurally in favor of releasing free radicals into the body.

Works Cited

Sayre, Hannah J., and Harsh Bhatia. “Innovative Way to Break Chemical Bonds Broadens Horizons for Making Molecules.” Nature, vol. 632, no. 8025, Nature Portfolio, Aug. 2024, pp. 508–9, https://doi.org/10.1038/d41586-024-02437-y. Accessed 10 Oct. 2024.

Tiefel, Anna F., et al. “Unimolecular Net Heterolysis of Symmetric and Homopolar σ-Bonds.” Nature, vol. 632, no. 8025, Aug. 2024, pp. 550–56, https://doi.org/10.1038/s41586-024-07622-7.