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The COVID-19 pandemic is putting the global health care system to the test. During this unprecedented time, the University of Arizona College of Pharmacy is working to make a difference in the fight against COVID-19 through research and training.

"Each one of us has to ask ourselves, 'What can we do to make a difference?'" said Jun Wang, an assistant professor in the college.

Wang has been studying respiratory viruses, including influenza, in his laboratory for several years. With the rise of COVID-19, his experience with antiviral treatments allowed him to quickly transition some of his ideas and laboratory resources to focus on new projects related to the pandemic. Within a period of two months, his lab was able to identify several promising drug candidates that inhibit SARS-CoV-2 virus in cell cultures.

"Everything has a starting point, and we're here to provide that starting point," Wang said. "What we discover may or may not be a drug, but we can identify chemicals that result in a drug. Pharmaceutical companies can then take over and continue the drug development work."

The pharmaceutical industry has undergone significant changes in the way it operates over the past 20 years, and these changes have opened up new avenues for academic research. Early drug discovery is now being shifted from companies to academic institutions and researchers like Wang.

In recent years, an increasing number of alliances and licensing deals have occurred between academia and the pharmaceutical industry. When Pfizer Inc., a multinational pharmaceutical corporation, came looking for a partner to test a series of compounds against SARS-CoV-2, the pathogen that causes COVID-19, they turned to the National Institute of Health's database of researchers. Wang, whose lab is funded, in part, through a grant from the NIH, was identified as the right person for the job.

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"All the big pharmaceutical companies and the NIH are trying to come up with a solution," Wang said. "(Pfizer) has a number of candidate molecules, which they think might be active against SARS-COV-2, but they don't have any biochemical assays set up to test their hypothesis. Through the introduction of NIH program officers, they came to know that my laboratory has developed those assays and approached us to test their molecules."

Other researchers nationwide are also finding ways to assist in the effort to develop a treatment. For years, Chris Hulme, a professor in the College of Pharmacy, has been working to identify novel treatments for Alzheimer's Disease. In recent weeks, he has shifted his efforts toward COVID-19.

"There remains a significant knowledge gap in the precise pharmacological underpinnings of COVID-19. As such, fundamental studies of signaling mechanisms involved in disease progression are required, which is typically the strength of academic research," Hulme said. "The deliverables of such efforts should unveil new biological targets, which medicinal chemists would be able to engage to deliver therapeutics that are small molecules and orally bioavailable. Efforts are also continuing to repurpose safe, existing drugs, which is heavily driven by academic researchers. In short, there is a broad spectrum of activities that academic researchers can impactfully engage to address this insidious pandemic."

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Jutta Wanner is co-director of the Arizona Center for Drug Discovery in the College of Pharmacy.

"The good thing about a university setting is that people truly work collaboratively," said Wanner, whose experience in the pharmaceutical industry includes positions at Roche, Lilly Forschung and BlinkBio. "From a chemistry perspective, you can tackle any disease because medicinal chemists are disease agnostic."

Facilitated by partnerships with academic drug discovery researchers, the pharmaceutical industry is testing different approaches to clear the virus. By the end of April, there were more than 200 clinical trials for COVID-19 registered in the U.S. alone. The timeline for drug development is lengthy and the process is research intensive; however, regulatory agencies are permitting accelerated measures to help speed the development of medications. The FDA, European Monitoring Centre for Drugs and Drug Addiction and China's Center for Drug Exploration are all using special emergency clinical trial approval processes for COVID-19, and a number of products are already moving through the systems.

"Where the timelines have been shortened are with companies that already had an antiviral drug in their pipeline for another disease," Wanner said. "Gilead's drug remdesivir comes to mind. All the preclinical de-risking for this compound had been done and safety had been established in humans."

Bench to Bedside

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"Right now, it feels like we're in the calm before the storm," said Christopher Edwards, assistant professor of pharmacy and clinical pharmacy specialist in emergency medicine at Banner – University Medical Center Tucson.

Hospital emergency departments are often the first stop for a COVID-positive patient, and clinical pharmacists like Edwards play an important role.

"We're here to make sure that during a challenging situation, good therapeutic decisions are being made," he said.

The medication use-process follows a straightforward path in a hospital. The patient's health care team reviews his or her status, sets appropriate goals and creates a therapeutic plan. Medications that are part of these therapeutic plans are ordered through the hospital pharmacy, where they are reviewed for accuracy, and then dispensed by a team of pharmacists. In an emergency department, when situations evolve rapidly, the system of checks and balances can break down.

"That's where mistakes get made," Edwards said. "In those situations, there is a lot of high energy and high stress, and having one person who is focused on the medication helps reduce the potential for errors."

In the era of COVID-19, health care workers are dependent on data collected through clinical trials to understand what immediate treatment options are available. Trained as medication experts, clinical pharmacists have spent the past several weeks evaluating literature to provide guidance on what drugs may be considered an effective and what may need more scrutiny.

"The challenging thing is to not get too excited or to suspend rigorous scientific methodology because something looks like it might be good," Edwards said. "The initial study that got the most attention looking at hydroxychloroquine and azithromycin only included six patients that received that medication combination, and while it did look promising, it didn't look at any clinical endpoints."

As the world waits for a cure, health care teams are able to offer their critically ill COVID-19 patients supportive care to treat symptoms.

"These patients will likely be in severe respiratory distress. They may need a ventilator, and that process requires a lot of medication use, especially if the patient is unstable," Edwards said. "We can make sure that the drugs the physicians are using are correct for those patients, that they are dosed effectively, and make sure they are readily available."

Embedded in the Community

Behind the counter of a local pharmacy, Theresa Taylor, a 1992 graduate of the College of Pharmacy class of 1992, makes it a habit to wipe down every surface she and her team have touched.

"Pharmacies tend to have regular sanitizing procedures," she said. "Now our efforts are heightened and intentional. I set my phone alarm to ring every 30 minutes to signal staff to wash hands and sanitize."

Approximately 67,000 pharmacies are open across the U.S., and more than 90% of U.S. residents live within 5 miles of a community pharmacy. In rural and medically underserved communities, pharmacists are often the only health care providers immediately accessible to patients.

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"You can walk into a pharmacy at any time, and ask anything you wish without an appointment or being charged a fee," said Nancy Alvarez, College of Pharmacy associate dean of academic and professional affairs for the Phoenix campus. "There is no other health professional that does that."

In the U.S., there are an estimated 13 billion pharmacy visits each year. Frequent interaction with the general public has placed community pharmacists at the center of public health initiatives.

Much of Taylor's day involves interacting with physicians and other primary care providers to advise on medication use and alternatives when a patient’s needs aren’t being met. In the past weeks, added attention on hydroxychloroquine and azithromycin has caused shortages across the country. For patients who rely on those medications, their local pharmacist may be the best advocate they have to work with physicians to identify alternatives.

In April, the U.S. Department of Health and Human Services issued a statement authorizing licensed pharmacists to order and administer FDA-authorized COVID-19 tests. The new guidance, issued under the Public Readiness and Emergency Preparedness Act, will expand testing capabilities in pharmacies, including some in Arizona.

For pharmacy professionals, whether they are behind the counter or in a lab, helping the public remain safe, healthy, and informed is critically important during this uncertain time.

"What is the motivation for us to come to work?" asks Wang. "Spending eight to 10 hours a day, six to seven days a week in the lab? For me, the motivation is, 'Can we make a difference?'"

A version of this story originally appeared on the College of Pharmacy website: https://www.pharmacy.arizona.edu/news/2020/drug-discovery-consultations-pharmacists-and-pharmaceutical-sciences-frontlines-covid-19.