Detecting the Next Threat

AACP Article

How are pharmacy schools taking lessons learned from the COVID-19 pandemic and applying them to research to identify and combat emerging pandemics?

By Joseph A. Cantlupe

As the COVID-19 pandemic wanes, resurges, lays low and sometimes intensifies, researchers at pharmacy and medical schools are playing a big role in examining ways to thwart the next waves of the coronavirus as well as other viruses that could evolve into pandemics. Academic institutions around the country are working diligently to assess potential threats already under exploration before 2020, with a focus on viruses impacting humans and animals. Researchers are carrying out these studies within and beyond the halls of academia, teaming up with industry and other partners to develop innovative programs to contain viruses before they spread uncontrollably.

The University of North Carolina Eshelman School of Pharmacy is concentrating on developing pills that can combat pandemic-level viruses like COVID-19 at its Anti-Viral Drug Discovery Center (AViDD). The university received a $65 million grant from the National Institute of Allergy and Infectious Diseases to run the program under its Rapidly Emerging Antiviral Drug Development Initiative (READDI).

Dr. Tim Willson, chief scientist of the Structural Genomics Consortium at the UNC Eshelman School of Pharmacy, and his lab team members are developing and opening sharing with the scientific community small molecule chemical probes of the dark proteome. He said the multidisciplinary effort fits nicely with the curriculum for student pharmacists and for other scientists working to engage with new antiviral therapies. The work is particularly illuminating for students, giving them an opportunity to experience all facets of the drug discovery process.

Willson is particularly pleased that their work, carried out by experts in medicinal chemistry, cell biology and chemical biology, is considered “open science,” meaning that their published findings are shared quickly throughout the world. “The drug molecules, data and everything we do in my lab goes on in the public domain,” Willson noted. “That’s one of the biggest drivers for me. What we’re doing is for society’s benefit. More drugs can be produced that way.”

He is quoted on UNC’s website: “Open Science guides the way we practice science and maintain the quality of our work. Openness is what sets SGC apart from other academic labs. Our goal is to distribute reagents and data without restrictions to the community and to enable other scientists to make immediate use of our discoveries. We deposit copies of all manuscripts on preprint servers as soon as they are ready for submission so that publication of our research is not delayed by the review process.”

One example of that effort, Willson said, involved the discovery of certain enzymes that appeared to be shutting down replication of the virus that causes COVID-19. He said the lab quickly published the information, making it widely available. READDI has also developed animal models to test inhibitors of alpha viruses, which include severe pathogens that attack the brain causing encephalitis and are often fatal. “We are making great progress with drugs that can block these viruses, which are found in many parts of the U.S., including North Carolina,” he said.



“Investment in antiviral drug discovery through open science is the best way to ensure that the world is prepared for the next pandemic.”

—Dr. Tim Willson

Preparation Through Partnerships

As a result of the “openness” in the university’s laboratory and science investigations, researchers have been able to draw many resources from industry partners, such as information from corporate libraries. The communication and interaction have accelerated the scientists’ efforts to move drug candidates into private development, according to university officials.

“This is great training for future scientists and for jobs in industry, and having cross-functional teams,” Willson said. “I do think students at the Center already are learning about the early drug discovery process and how you pick a target, how you build assays and find compounds, or if you want to work with disease models. This is a great opportunity for scientists in all aspects.”

Willson’s career has bridged the gap between academia and pharmacy. For nearly 30 years he worked for GlaxoSmithKline (GSK) as director of chemical biology. “This is how we work all the time, as a multidisciplinary team,” he said. “It makes sense [to work this way] to move the drug along.”

At UNC, a nearby lab is run by Dr. Ralph Baric, a professor in the Department of Microbiology and Immunology and cofounder of READDI. He is a world leader in the study of coronaviruses, and for decades he warned that they represented a “significant and ongoing global health threat, particularly because they can jump, without warning, from animals into the human population and they tend to spread rapidly.” The World Health Organization indicates that other pathogens being studied by READDI, such as filoviruses including Ebola and Marburg, also have the potential to cause the next pandemic.

The READDI-AViDD Center, one of nine established by the National Institutes of Health, is a public private partnership with an “interdisciplinary team of experts,” including from the Gillings School of Global Public Health at UNC, the university said. Carolina’s Creativity Hubs Initiative and the Eshelman Institute for Innovation and the North Carolina General Assembly financed the program. The university said in a statement that it will conduct research on early stage identification and validation of novel viral targets, with an eye toward identifying small molecules and biotherapeutics that directly block viral threats.

“We have to do a much better job of modeling these infectious diseases, incorporating economic behaviors, which many epidemiologic models miss.”

—Dr. Anirban Basu

The Center’s international collaborators include the University of Toronto; Diamond Light Source LTD; Sichting VU; Duke University; McGill University; Rutgers University; the University of Alberta; the University of Wisconsin-Madison; University College London; and Vanderbilt University and the Vanderbilt University Medical Center. Willson said the collaborators often have discussions to evaluate the process of drug discovery. “Investment in antiviral drug discovery through open science is the best way to ensure that the world is prepared for the next pandemic,” he emphasized.

The research is particularly important because it comes at a time when, despite the progress in vaccine research and development, R&D for therapeutics and diagnostics for pathogens and pandemic potential remain underfunded and lagging, according to the Third Implementation Report from the 100 Days Mission. The mission, which stemmed from a 2022 global pandemic preparedness summit cohosted by the Coalition for Epidemic Preparedness Innovations and the UK government, strives for availability of “diagnostics, therapeutics and vaccines” within the first 100 days of a pandemic threat.

On Alert for Potential Risks

Deaths from a handful of viruses that spill over from animals to humans may increase “12-fold by 2050” because of “climate change and habitat encroachment,” according to the British Medical Journal. While there is much examination of the biology of infectious diseases, scholars also tout the importance of reviewing the economic impacts, especially after seeing the pandemic’s ramifications on the world’s economic markets since March 2020.

“The pandemic has evolved quite a bit,” said Dr. Anirban Basu, director of The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, which is part of the University of Washington School of Pharmacy. “We have to do a much better job of modeling these infectious diseases, incorporating economic behaviors, which many epidemiologic models miss.” One of his students, Felipe Montano-Campos, a third-year Ph.D. candidate at the CHOICE Institute, is doing just that, working on a paper that explores how people have reacted to information and perceived risks from the coronavirus. His dissertation examines the economic epidemiology of infectious diseases, with a concentration on COVID-19.

“It is important to focus on biological factors but also to create models regarding how people react to information (about COVID-19) and how they perceive risks,” Montano-Campos said. The paper’s focus is on lessons learned from public and government actions during COVID-19 and how to incorporate them in potential solutions to combat future pandemics. Montano-Campos said he is examining how government preventive practices and people’s responses have changed over time.

One of Basu’s colleagues, Dr. Deborah Fuller, professor of microbiology at the University of Washington School of Medicine, had been working on developing vaccines and antivirals prior to the pandemic. “There’s always going to be another pandemic as long as humans and animals are living in the world together,” Fuller said, “as has happened throughout time and history. What COVID-19 did was bring it out to the forefront for society. We must be more prepared than ever—COVID-19 has helped us develop some of those tools and now we apply those and hopefully we will be in a better situation to stem the next pandemic.”

She is among the scientists investigating what she termed a universal vaccine for flu and also coronaviruses. The goal would be to provide a high level of immunity regardless of changes to the virus. The idea is to “induce a level of immunity in the population so that any new virus is not going to have a dramatic effect in terms of severity of disease or spread among people,” she explained. While there are vaccines against COVID-19, advances have not come that far with some other emerging threats. Collaboration between schools within universities is key to moving the science forward on drug discovery and vaccines.

Fuller is working on new technology to protect against emerging infectious diseases, such as fungi. She and other scientists from the University of Washington School of Medicine and Northern Arizona University, with the Washington National Primate Research Center, received a $1.5 million grant from the National Institute of Allergy and Infectious Diseases to fund research for a vaccine for Valley Fever, a fungal infection that Fuller said is spreading in hot and dry regions.

The NIH has been tasked with creating a vaccine for Valley Fever within the next decade. The disease is endemic in the Southwest and the fungus is in the soils, often stirred by forest fires, she continued. It can be particularly harsh to humans and dogs, impacting the nervous system. In this project and others, Fuller focuses her instruction on a “marriage between disciplines” that she believes will continue to affect the work of medical and pharmaceutical scientists for years to come as they try to prepare for the next pandemic.

Joseph A. Cantlupe is a freelance writer based in Washington, D.C.