A team comprising researchers from UTEP and the historically Black research university in Washington, D.C., discovered valuable data in comparing the fundamental mechanisms of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2 — also known as COVID-19 — to better understand how these viruses attack the human body. Their findings are published in an article titled “Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind with Human ACE2” that recently appeared in the scientific journal Frontiers in Molecular Biosciences.

“We are very excited and interested in the timely work that Dr. Li and his collaborators have reported,” said Robert Kirken, Ph.D., dean of UTEP’s College of Science. “As the SARS-COV2 continues to evolve through its passage by infected humans, the rapid identification and assessment of these mutants using the research and testing approaches they have established will be critically important for the development of new vaccines and therapeutics.”

In comparing the viruses, researchers found that both are very similar in sequence and almost identical in structure. Using computational approaches, they were also able to identify mutations of SARS-CoV that make SARS-CoV-2 significantly more contagious and prone to cause serious infections.

“We found that because of mutations, the binding from SARS-CoV-2 to the human cell is much stronger compared with SARS-CoV,” Li said. “This might be one of the reasons why SARS-CoV-2 is spreading much faster and is difficult to control. SARS-CoV-2 also uses a much smarter strategy to attack the human cell than SARS-CoV. For example, when SARS-CoV infects or binds to the human cell, it uses several key residues or amino acids to do so, while SARS-CoV-2 uses more residues, making it more robust and easier to completely hijack the human cell.

“We identified the most important residues for SARS-CoV-2 to bind to the human cell. This type of data is key for drug development to cure or treat infections caused by these types of viruses. These fundamental rules and features can also be used for future disease control when perhaps 10 years from now, there’s a SARS-CoV-3 or 4.”

Researchers from both universities focused on examining one of the virus’ four main proteins, known as the spike protein, that initiates infection to the human body. They discovered that from SARS-CoV to SARS-CoV-2 there is an interesting change in mechanism of the binding domain of the spike protein.

“The binding domain needs to flip out so that it can bind to the human cell, but we found some strange mutations that happened. Like the hinge of a door, the binding domain may affect the flip mechanism of SARS-CoV-2. It may be more flexible, making it easier to bind to the human cell,” Li said.

The team included an interdisciplinary mix of undergraduate and graduate students, postdoctoral researchers and faculty from both UTEP and Howard University. Yixin Xie, a UTEP graduate student and research assistant, served as the paper’s first author, and led the calculation and analysis portions of the project while working closely with other UTEP and Howard University students remotely due to the pandemic.

In the future, the goal of the team is to expand their research to study the mechanisms of all four proteins to better understand the inner workings of these viruses even more to help combat COVID-19 and related viruses.

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The study, performed on mice induced with a model of MS and the first to investigate IndCl’s effect on the pathology and function of the complete afferent visual pathway, is published in Brain Pathology. The afferent visual pathway includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

In MS, a disease in which the immune system “demyelinates” or eats away at the protective covering of nerves, the initial period of inflammation and demyelination often damages the optic nerve and other parts of the visual system first. As a result, approximately 50% of patients with MS experience optic neuritis — inflammatory demyelination of the optic nerve — prior to showing initial symptoms. Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.

The optic nerve, a heavily myelinated bundle of nerves located at the back of the eye, transfers visual information from the retina to the vision centers of the brain through electrical impulses. Myelin acts as an insulating substance that speeds the transmission of these electrical impulses. Partial myelin loss slows transmission of visual information; severe myelin loss may stop the signal altogether.

The researchers used IndCl to assess its impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.

“IndCl has been previously shown in mice to reduce motor disability, increase myelination, and neuroprotection in the spinal cord and corpus callosum,” said Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study’s lead author. “Its effects in the visual system, however, were not evaluated until now. Our study shows the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, are able to restore some function with IndCl treatment with successful attenuation in inflammation and an increase in remyelination.”

The visual pathway in mice is similar to that in humans. The mouse brain is, therefore, an excellent model for scientists to study vision impairment. In the lab, Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice. At the end of the experiment, they performed functional assay to measure the visual electrical signal; and immunohistochemistry to examine the visual pathway. The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.

For Tiwari-Woodruff, the next question is how IndCl treatment induces functional remyelination in the visual pathway. Her lab, in collaboration with the lab of co-author John A. Katzenellenbogen at the University of Illinois at Urbana-Champaign, is investigating new drugs that are analogues of IndCl.

“Measuring visual function and recovery in the presence of novel therapies can be used to screen more effective therapies that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage,” Tiwari-Woodruff said.

Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.

“We treated the MS mice with IndCl at peak disease,” Tiwari-Woodruff said. “If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There’s a point of no return. Our paper stresses that to acquire vision improvement, treatment must start early. Early treatment can recover 75%-80% of the original function.”

Tiwari-Woodruff stressed that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.

“There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS,” Tiwari-Woodruff said. “Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good estrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment.”

The counterintuitive finding highlights the influence of airborne particles, or aerosols, that block incoming sunlight. When emissions of aerosols dropped last spring, more of the Sun’s warmth reached the planet, especially in heavily industrialized nations, such as the United States and Russia, that normally pump high amounts of aerosols into the atmosphere.

“There was a big decline in emissions from the most polluting industries, and that had immediate, short-term effects on temperatures,” said NCAR scientist Andrew Gettelman, the study’s lead author. “Pollution cools the planet, so it makes sense that pollution reductions would warm the planet.”

Temperatures over parts of Earth’s land surface last spring were about 0.2-0.5 degrees Fahrenheit (0.1-0.3 degrees Celsius) warmer than would have been expected with prevailing weather conditions, the study found. The effect was most pronounced in regions that normally are associated with substantial emissions of aerosols, with the warming reaching about 0.7 degrees F (0.37 C) over much of the United States and Russia.

The new study highlights the complex and often conflicting influences of different types of emissions from power plants, motor vehicles, industrial facilities, and other sources. While aerosols tend to brighten clouds and reflect heat from the Sun back into space, carbon dioxide and other greenhouse gases have the opposite effect, trapping heat near the planet’s surface and elevating temperatures.

Despite the short-term warming effects, Gettelman emphasized that the long-term impact of the pandemic may be to slightly slow climate change because of reduced emissions of carbon dioxide, which lingers in the atmosphere for decades and has a more gradual influence on climate. In contrast, aerosols — the focus of the new study — have a more immediate impact that fades away within a few years.

The study was published in Geophysical Research Letters. It was funded in part by the National Science Foundation, NCAR’s sponsor. In addition to NCAR scientists, the study was co-authored by scientists at Oxford University, Imperial College, and the University of Leeds.

Teasing out the impacts

Although scientists have long been able to quantify the warming impacts of carbon dioxide, the climatic influence of various types of aerosols — including sulfates, nitrates, black carbon, and dust — has been more difficult to pin down. One of the major challenges for projecting the extent of future climate change is estimating the extent to which society will continue to emit aerosols in the future and the influence of the different types of aerosols on clouds and temperature.

To conduct the research, Gettelman and his co-authors used two of the world’s leading climate models: the NCAR-based Community Earth System Model and a model known as ECHAM-HAMMOZ, which was developed by a consortium of European nations. They ran simulations on both models, adjusting emissions of aerosols and incorporating actual meteorological conditions in 2020, such as winds.

This approach enabled them to identify the impact of reduced emissions on temperature changes that were too small to tease out in actual observations, where they could be obscured by the variability in atmospheric conditions.

The results showed that the warming effect was strongest in the mid and upper latitudes of the Northern Hemisphere. The effect was mixed in the tropics and comparatively minor in much of the Southern Hemisphere, where aerosol emissions are not as pervasive.

Gettelman said the study will help scientists better understand the influence of various types of aerosols in different atmospheric conditions, helping to inform efforts to minimize climate change. Although the research illustrates how aerosols counter the warming influence of greenhouse gases, he emphasized that emitting more of them into the lower atmosphere is not a viable strategy for slowing climate change.

“Aerosol emissions have major health ramifications,” he said. “Saying we should pollute is not practical.”

Single-celled organisms in the open ocean use a diverse array of genetic tools to detect light, even in tiny amounts, and respond, according to a study published Feb. 1 in the Proceedings of the National Academy of Sciences.

“If you look in the ocean environment, all these different organisms have this day-night cycle. They are very in tune with each other, even as they get moved around. How do they know when it’s day? How do they know when it’s night?” said lead author Sacha Coesel, a research scientist in oceanography at the UW.

Though invisible to the human eye, ocean microbes support all marine life, from sardines to whales. Knowing these communities’ inner workings could reveal how they will fare under changing ocean conditions.

“Just like rainforests generate oxygen and take up carbon dioxide, ocean organisms do the same thing in the world’s oceans. People probably don’t realize this, but these unicellular organisms are about as important as rainforests for our planet’s functioning,” Coesel said.

By analyzing RNA filtered out of seawater samples collected throughout the day and night, the study identifies four main groups of photoreceptors, many of them new. This genetic activity uses light to trigger changes in the metabolism, growth, cell division, movements and death of marine organisms.

The discovery of these new genetic “light switches” could also aid in the field of optogenetics, in which a cell’s function can be controlled with light exposure. Today’s optogenetic tools are engineered by humans, but versions from nature might be more sensitive or better detect light of particular wavelengths, the researchers said.

“This work dramatically expanded the number of photoreceptors — the different kinds of those on-off switches — that we know of,” said senior author Virginia Armbrust, a UW professor of oceanography.

Not surprisingly, many of the new tools were for light in the blue range, since water filters out red wavelengths (which is why oceans appear blue). Some were also for green light, Coesel said.

The researchers collected water samples far from shore and looked at all genetic activity from protists: single-celled organisms with a nucleus. They filtered the water to select organisms measuring between 200 nanometers to one-tenth of a millimeter across. These included photosynthetic organisms, like algae, which absorb light for energy, as well as other single-celled plankton that gain energy by consuming other organisms.

The team collected samples every four hours, day and night, for four days in the North Pacific near Hawaii. Researchers used trackers to follow the currents about 50 feet (15 meters) below the surface so that the samples came from the same water mass.

The study also looked at samples that came from a depth of 120 and 150 meters (400 and 500 feet), in the ocean’s “twilight zone.” Even there, the genetic activity showed that the organisms were responding to very low levels of sunlight.

While the sun is up, these organisms gain energy and grow in size, and at night, when the ultraviolet light is less damaging to their DNA, they undergo cell division.

“Daylight is important for ocean organisms, we know that, we take it for granted. But to see the rhythm of genetic activity during these four days, and the beautiful synchronicity, you realize just how powerful light is,” Armbrust said.

Future work will look at places farther from the equator, where plankton communities are more subjected to the changing seasons.