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Delaware researchers, companies helping study COVID-19, find ways to treat it

Delaware’s academics and bio-pharmaceutical industry have stepped up in the fight against the COVID-19 virus, leading studies that seek to better understand the threat while also trying to develop better testing and treatment options.

In late May, the Newark-based National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) announced it has been granted $9 million in COVID response funding from the Department of Commerce. The funds will help Delaware scientists and engineers grow vaccine-manufacturing capacity and expand testing and diagnostic capabilities.

“The scary truth is that the United States is currently not ready to mass-produce a vaccine for COVID-19, even once we’ve developed one, and that’s a problem we need to fix right away,” said Sen. Chris Coons in response to the announcement. “I’m thrilled that Delaware scientists and engineers at NIIMBL will be leading that effort.”

UD researchers work to find virus’ weaknesses

Juan Perilla and Jodi Hadden-Perilla are working with a HBV Capsid that works to destroy the Hepatisis B virus. | Photo c/o University of Delaware

Juan Perilla and Jodi Hadden-Perilla, assistant professors at the University of Delaware’s Department of Chemistry and Biochemistry, are no strangers to the study of viruses, having studied  hepatitis B and HIV for more than a decade.

In late March, the professors were approved for a $200,000 National Science Foundation (NSF) grant to study the molecular biology of SARS-CoV-2, the official name of the virus that causes COVID-19 and has infected millions worldwide. The one-year grant was approved through the NSF’s Rapid Response Research program, which is only used in emergencies.

The duo’s work won’t directly lead to the development of a vaccine, which requires researchers to find a way to get a person’s body to recognize the virus and attack it to prevent an infection, Perilla explains. It is more likely to aid in the development of antiviral drugs, which can help kill the virus in an already infected person.

“We’re like step zero in the process,” he says. “If you know how any machine works, you have a better chance to know how to stop it.”

The researchers’ goal is to identify weaknesses in the virus that scientists could tailor their treatments to exploit. By altering the chemistry and changing its physics, a treatment could stop the lifecycle of the virus.

Perilla estimates preliminary findings will likely come this summer.

Perilla and Hadden-Perilla are working with Tyler Reddy, a computa-tional virologist at Los Alamos National Laboratory in New Mexico, on the project, which also has seven other researchers assigned to it. 

The researchers are working seven days a week, meeting via videoconferencing to derive new analysis tools or software while remotely connecting to their UD labs or the Frontera supercomputer at the Texas Advanced Computing Center at the University of Texas at Austin, where they run theoretical simulations of the virus.

There are currently eight identified strains of SARS-CoV-2 around the world, but Perilla’s research team is only working on one of them. His experience in working with HIV, which also has many different strains, has shown that differences between strains are often subtle, and creating a final model of one strain allows researchers to detect the differences more quickly, Perilla explains.

“It’s definitely better than starting from zero,” he adds. 

Incyte seeks to repurpose blockbuster drug

Global biopharmaceutical company Incyte announced in early April that it was studying whether it could repurpose its blockbuster drug Jakafi to aid in the treatment of COVID-19 patients.

The company reported that it was launching phase 3 clinical trials, with the assistance of the U.S. Food & Drug Administration (FDA), to study the effectiveness of its drug, known generically as ruxolitinib.

Ruxolitinib is approved by the FDA for the treatment of myelofibrosis and polycythemia vera, part of a group of rare blood cancers, as well as for steroid-refractory acute graft-versus-host disease.

Ruxolitinib blocks the signaling of cytokine in the JAK-STAT pathway and may be effective in preventing potentially life-threatening cytokine storms and consequent organ failure. Cytokine storm is a severe overreaction of the immune system that can be caused by a viral infection, autoimmune condition, or other disease.

Because many COVID-19 patients with severe respiratory disease, such as pneumonia, have symptoms consistent with cytokine storm and increased activation of the JAK-STAT pathway, it is hypothesized that ruxolitinib may be able to play a role in treating these patients, Incyte reports.

“Our intent is to build on emerging evidence from independent studies to further establish the role ruxolitinib could play in balancing immune response to the infection and therefore potentially improving outcomes of patients with COVID-19-associated cytokine storm,” said Dr. Steven Stein, chief medical officer for Incyte, in a statement.

While an Incyte spokesperson said the company could not estimate how long the clinical trial would take, she said “enrollment may be quick, and we intend to share the results as soon as possible after the study is complete.”

ChristianaCare looks into treatment of future outbreaks

Shirin Modarai, Ph.D., research scientist, Sambee Kanda, MS, research assistant, Eric Kmiec, Ph.D., director | PHOTO C/O CHRISTIANACARE

Eric Kmiec, Ph.D., director of the Gene Editing Institute of the Helen F. Graham Cancer Center & Research Institute at ChristianaCare, has been leading the New Castle County-based health system’s effort to study patients’ responses to the COVID-19 virus.

The Gene Editing Institute is well-known in the nation for its work with CRISPR, an emerging technology that allows scientists to examine genetic defects and treat them at a level not seen in prior decades. 

“It helps us correct inherited diseases like cystic fibrosis or sickle cell disease, but it will also help us to disable genes that are malfunctioning in cancer,” Kmiec says, noting that ChristianaCare’s work to date is aimed at lung and pancreatic cancer.

In mid-May, the Gene Editing Institute was contacted by a consortium of researchers at Stanford University, the University of California Berkeley and several biotechnology companies to join an effort that is seeking to determine which genes are responding to a COVID-19 infection.

“That’s really the problem in the country right now. Some people who get infected remain asymptomatic while others have a variety of levels of response,” Kmiec says.

Researchers will study gene panels obtained from COVID-19 patients, likely through saliva or blood samples, to seek out the genes that may be influencing a patient’s response to the virus. Once they can determine the genes, scientists may be able to identify factors related to those genes, such as genetic ancestry, inherited diseases and socioeconomic factors.

If the work is successful, Kmiec says CRISPR tests may one day be able to tell hospitals how an individual patient may fare with the virus early on in their diagnosis, potentially leading to better allocation of resources and treatment of patients.

Because the study will likely require a year of testing of patients, Kmiec says, it is unlikely to be used in response to the COVID-19 pandemic. But because COVID-19 is among the SARS family of coronaviruses, which already saw a prior pandemic in 2002, epidemiologists believe there will likely be more such pandemics in the future where the CRISPR science could be applied.

Kmiec says his team is “cautiously optimistic that we’ll be able to come up with something in the next year or so that will help us understand what genes are accounting for the response.” 

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