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The long game: UVa researchers shift focus to COVID-19

When the pandemic came to the country’s shores, University of Virginia Medical School researchers studying the life cycles of various viruses dropped their cultures and switched gears.

UVa laboratory leaders, building upon studies by researchers across the world, are working on possible vaccines, screening existing drugs for efficacy and studying the use of antibodies in fighting SARS-CoV-2, the novel coronavirus that causes the COVID-19 disease that has swept the globe.

“A lot of our research is on emerging infectious diseases, like different strains of influenza,” said Dr. Paul Kasson, who conducts virus research at the medical school. “We think of [influenza] as an old disease, but it’s the case model for infectious respiratory diseases. We had a lot of information and research that could be applied to [SARS-CoV-2].”

Kasson, Dr. William Petri and Dr. Steven Zeichner are among university researchers who moved their research from one virus to another.

“We saw that COVID-19 was going to be a big deal and thought we should get a head start on that,” Kasson recalled. “We started preparatory work to switch over in late January. It changed for us what we were doing specifically but the ideas and the approach we use in fighting influenza apply to this.”

Zeichner, who has been studying potential treatments and vaccines for HIV, has adapted research models to address the new coronavirus.

“Since it was such an imperative problem and we had a window where we could move over and apply our research to it, we thought we had an obligation to do so,” Zeichner said.

Using the results of others to model the new virus, Zeichner said he and his colleagues saw some similarities in the protein structures of HIV and SARS-CoV-2. The proteins, while structured differently, are used by both viruses to commandeer cells and replicate.

Like other coronaviruses, SARS-CoV-2 particles are spherical and have spiked proteins that stick out from their surfaces; the spikes latch onto human cells, allowing the viral membrane to fuse with the cell membrane and create copies of the virus.

His group’s research into vaccines and anti-viral drugs for HIV now is being applied to the novel coronavirus

“We know a lot about the virus. We know its structure. Researchers in China got the structure very fast and put it online in a matter of six weeks,” Zeichner said. “If you have the sequence of the virus, you can do a lot.”

“Everyone in the world is working on this and we’re learning a lot about the virus as we go,” Kasson said. “We started out with informed guesses and as we sequence it and gain more data, some of those guesses are supported and some aren’t. That seems to change a bit every day as more research is being done and shared. We have to keep in mind the difference between our best guesses and those things we learn for sure.”

Research is designed to prove and disprove best guesses and the university’s medical school has a strong research game. Last fiscal year its research teams snagged a record $146.3 million in funding from the National Institutes of Health.

The funding has put dollars behind ambitious research efforts to pioneer new treatments, such as an artificial pancreas developed at UVa, as well as delving into the mysteries of what causes diseases and how to treat or cure them.

University officials credited the talent and abilities of staff and faculty for earning the grants.

“The NIH is the nation’s single greatest resource for funding of bio-medical research and the quantity of grants is relative to the quality of the research programs,” said Dr. David S. Wilkes, dean of the medical school. “The grants are incredibly competitive to get. They want to know the work that researchers propose is likely to succeed. We’re at a record level of funding and that’s a testament to the abilities of our faculty and the quality of their work.”

NIH funding has helped UVa pioneer using focused soundwaves rather than scalpels in surgery, develop new cancer treatments and the recent milestone of an artificial pancreas to assist those with Type 1 diabetes.

On March 25, the NIH issued an emergency competitive revision to existing NIH awards to allow researchers to refocus on the current pandemic.

The NIH “is particularly interested in projects focusing on viral natural history, pathogenicity, transmission, as well as projects developing medical countermeasures and suitable animal models for pre-clinical testing of vaccines and therapeutics against SARS-CoV-2/COVID-19,” the revision states.

“Transmission characteristics and the associated morbidity and mortality are not completely understood, but there is clear evidence of human-to-human transmission,” the revision notice states. “Many other aspects of viral pathogenesis, natural history and host range are poorly understood. Given this, there is an urgent public health need to better understand SARS-CoV-2/COVID-19.”

Although SARS-CoV-2 and HIV are completely different types of viruses, the fact that both utilize a particular protein to access host cells and replicate gives researchers a leg-up on the illness.

“If we take our research into HIV and can see similar structures in this virus, that gives us some options to work on based on our previous research,” Zeichner said. “We’re working with other labs across the state. People are working hard.”

“We’re looking at what can be done in the short term as far as treating symptoms and anti-virals, but also in the long term as far as creating vaccines,” Kasson said. “There has been a lot of research on SARS and MERS, which have some similarities to SARS-CoV-2. There’s a lot of ground work out there. Some of it will apply to this situation and some of it won’t. There’s a lot of information to work off of.”

“There have been other problematic coronaviruses so there is a lot known about some particulars,” Zeichner agreed. “People are working hard everywhere. I feel lucky working for the university because, even though they have shut down much of the research that normally goes on due to social distancing requirements, they’ve agreed to keep some of the larger machinery operating so we may use some important equipment we need.”

“The hope is with all of the capability we have in the country we could come up with ways to help control the spread and come up with better treatments,” Kasson said. “The long game is better anti-virals and an effective vaccine. That’s what we’re working toward.”


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