Viral Analysis: Vet Med acknowledged for scientific achievement in COVID research

Viral Analysis: Vet Med acknowledged for scientific achievement in COVID research

Tuesday, October 8, 2024

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In the past 10 years, only 11 Oklahoma State University researchers have had their research published in the prestigious journal, Science.

The most recent, and the first in the College of Veterinary Medicine's history, is Dr. Xufang Deng, assistant professor in the Department of Physiological Sciences.

Deng has been studying coronaviruses for nearly 13 years. He began studying them while completing his postdoctoral training at Loyola University Medical School in Chicago. During this time, there was an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV). It was first identified in Saudi Arabia and quickly spread across the Middle East and eventually into Africa and South Asia. Although it never escalated to a pandemic, many lives were lost amidst the outbreak.

This inspired Deng to dedicate his studies to coronaviruses.

Coronaviruses are a large family of viruses that cause diseases ranging from the common cold to COVID-19. They are also zoonotic, which means they can be transmitted from animals to humans. This family of viruses commonly affects the respiratory system, but can also affect other parts of the body as well, particularly the gastrointestinal tract.

Deng's research interests include understanding the molecular details of coronaviruses that cause diseases and developing antiviral interventions to prevent or treat those diseases.

At the start of the pandemic, Deng began studying SARS-CoV-2. While the pandemic has largely faded from public attention, the virus continues to spread, mutate and cause both acute illness and long-term COVID. Only a few antiviral drugs are available, and each have different limitations: some are not available to patients with underlying conditions, and some have drug-to-drug interaction risks. Additionally, multiple antiviral options are needed to reduce the risk of selecting drug-resistant variants.

Deng and his team of researchers sought to develop an additional treatment option. The two essential proteases, or enzymes, that facilitate replication of SARS-CoV-2 are Mpro and PLpro. Mpro is the main protease and the primary target of drugs that are currently being used clinically. PLpro is a viral papain-like protease that all coronaviruses have and is required for the virus to spread. Its commonality among coronaviruses leads many researchers to pursue this target despite it being challenging.

In this study, Deng and his collaborators at Rutgers University designed and synthesized 85 noncovalent PLpro inhibitors that bind to a recently discovered binding site. From the group, they found one in vivo lead Jun12682 inhibited SARS-CoV-2 and its variants. In a SARS-CoV-2 mouse model, oral treatments with Jun12682 improved mouse survival and reduced viral loads and lesions in the lungs. This success suggests PLpro inhibitors are promising options for SARS-CoV-2 antiviral drugs.

"I hope that our PLpro inhibitor will eventually become a widely available treatment option for the general population," Deng said. "It could serve as an alternative to current drugs or be used in combination therapy to reduce side effects and the risk of drug resistance."

Developing alternative drug options is essential in preventing resistance from developing.

"Our published drug is the first in its class to show antiviral efficacy in vivo, which is a milestone for PLpro inhibitor research," Deng said.

Deng's lab continues to make improvements to the drug, including reducing dosage to minimize side effects, adjusting dosing frequency and expanding the dosing window to allow for delayed treatment.

"Our goal is to develop a safe and effective drug that can be taken orally, even when individuals feel sick enough to realize they need medication," Deng said.

Deng said they are also researching broad-spectrum PLpro inhibitors capable of blocking a range of zoonotic coronaviruses with pandemic potential. Additionally, they are exploring combination therapy with other drugs and studying viral drug resistance, which is a crucial step for designing future inhibitors.

Deng's study, titled "Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model," was published in the journal, Science, earlier this year.

Research is a continuous and challenging process. Deng said being published in Science validates all the hard work and dedication that went into his studies.

"The most exciting aspect for a scientist is the realization that their efforts and passion have made a tangible impact on advancing science and benefiting humanity," Deng said.

Deng said results such as this are why he is a researcher.

"I love science and enjoy doing research," Deng said. "When my research becomes more impactful and drives the science forward - that's my dream."

Deng said that when science moves forward and leads to better options for treating and helping people, it further validates why he enjoys being involved.

This study also demonstrates a collaborative effort across the OSU campus and at other universities. Other researchers from the CVM, such as Dr. Alex Ford, assistant professor of veterinary pathobiology, and members of the immunopathology core of the Oklahoma Center for Respiratory and Infectious Diseases were involved.

"Without multidisciplinary collaboration and strong support from the OSU research infrastructure, achieving this milestone would not have been possible," Deng said.

This is a considerable step in COVID-19 research and an important part of the One Health mission.

"Dr. Deng is an incredible asset to our college and the One Health mission," said Dr. Carlos Risco, College of Veterinary Medicine dean. "He continues to make advancements that positively contribute to treating and solving prevalent human and animal health issues."

Deng said from the perspective of a coronavirologist, coronavirus diseases exemplify the One Health concept because they are ubiquitous in nature and affect domestic and wild animals as well as humans. These viruses' pervasive presence demonstrates the need for collaborative efforts across disciplines to understand and mitigate the spread of disease.

"With increasing human-environment interaction, the risk of cross-species transmission has significantly risen," Deng said. "It is imperative to study coronaviruses using the One Health approach to comprehend virus transmission, disease biology and develop interventions tailored to each aspect of the One Health concept."

Deng's lab will continue to collaborate with partners across campus and at other universities to develop treatments, vaccines and solve issues related to human, animal and environmental health.

"We are immensely proud of Dr. Deng and Dr. Ford's publication in Science," Risco said. "This achievement represents a culmination of hard work and dedication to bettering the lives of people, animals and the planet."

Photo By: Taylor Bacon and Elizabeth Perdue

Story By: Taylor Bacon | Research Matters Magazine