The key to fighting viruses: Understanding their structure is vital to unlock a healthy future for humanity

Richard Kuhn

Richard Kuhn, a molecular virologist at Purdue University, works to map out virus vaccines ahead of potential pandemics. (Purdue University photo/Kelsey Lefever)

WEST LAFAYETTE, Ind. — There is no cure for the common cold. But there are cures — or at least vaccines — for other viruses, and researchers are working hard to build a toolbox to be able to rapidly develop vaccines for new and emerging viruses.

Viruses are so small that tens of millions of them can fit on the head of a pin. Understanding, let alone fighting, something so infinitesimally small is a crowning challenge of modern medicine.

The physical structure of its molecules dictates how a virus infects people and moves through their bodies as well as how to formulate effective vaccines and treatments.

That physical structure is precisely the expertise of molecular virologist Richard Kuhn, the Trent and Judith Anderson Distinguished Professor in Science in Purdue University’s College of Science and Krenicki Family Director of the Purdue Institute of Inflammation, Immunology and Infectious Disease. He is harnessing that expertise to lay the groundwork for engineering vaccines for a range of viruses.

“The core of what we do is to do analyze and study the structures of viruses and antibodies,” Kuhn said. “We are working to understand what the important features of an antibody are that make it effective at neutralizing — blocking — the virus.

As part of the team that in 2017 mapped the structure of a human antibody that could potently block Zika virus, Kuhn is one of the foremost scouts in the fight against viral diseases.

Viral threats: Tiny entities, big problems

A virus is, arguably, the smallest possible living thing. It is a bundle of DNA or RNA bound up in a minuscule core, sometimes surrounded by a sturdy envelope and sometimes not. It can reproduce, but not by itself. It relies on an outside partner to reproduce: a plant, animal or even a fungus.

In his lab in Purdue’s Department of Biological Sciences, Kuhn studies specifically RNA viruses, particularly those spread by mosquitoes and ticks, including alphaviruses like chikungunya and eastern equine encephalitis, and flaviviruses like Zika, dengue fever, West Nile and yellow fever. His research involves studying the structure of viruses and how they interface with the cells of their hosts’ bodies — hence the mapping of the Zika antibodies.

That structural understanding is key to being able to create vaccines and treatments for viruses.

“With the experience during the pandemic, there is more of a focus on viruses globally,” Kuhn said. “Since the 1970s, at least, there has been a steady stream of known and emerging viruses, including HIV, Ebola and, of course, influenza comes back every year, sometimes with significant effect.”

As climate change increases temperatures and the world becomes more global and interconnected, viruses become more prevalent and have vastly more opportunities to mutate and jump from animal to human hosts. Thus many tick- and mosquito-borne diseases like the ones Kuhn studies are becoming more of an outbreak risk.

The SARS-CoV-2 virus, the cause of the COVID-19 pandemic, is a coronavirus. Before the emergence of SARS-CoV-2, doctors and researchers were already familiar with other coronaviruses and were well on their way to understanding how to build a vaccine for COVID-19. That’s in part why research teams were able to develop effective vaccines so quickly. But all sorts of viruses cause outbreaks and epidemics — not just coronaviruses. Flaviviruses, carried by ticks and mosquitoes, might very well be among the next epidemics humanity faces.

“Despite all the human tragedy, SARS-CoV-2 was a relatively simple target in terms of quickly developing a very effective vaccine,” Kuhn said. “There were features of the virus that made developing a vaccine relatively easy. The next pandemic may not be like that. It’s not going to be like in the movie ‘Contagion,’ where they develop a vaccine in two weeks. The more work we can do now, the more it will pay off in case of a novel pandemic.”

His team may not be crossing the bridge before they come to it, but they’re certainly amassing the timbers and bolts and drawing up the plans.

A close-up of a petri dish containing a pile of EM grids, which look like 5 millimeter disks of various metals with colorful centers.
These small jewellike disks are EM grids. They are how molecular virologists like Richard Kuhn are able to physically look at viruses using massive cryo-electron microscopes. (Purdue University photo/Kelsey Lefever)

“The whole idea here is to understand what we need to do in order to develop a vaccine against known and unknown viruses in this group,” Kuhn said. “We are not developing any specific vaccine for any one virus; we are developing platforms so that when the next virus comes along, we’ll be able to rapidly develop an effective vaccine for it.”

Unlocking vaccines: Better tools bring faster solutions

Kuhn is harnessing his expertise in partnership with a new multicenter grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). The effort, led by viral expert Michael Diamond of the Washington University School of Medicine in St. Louis, alongside Kuhn, is part of NIAID’s new Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) network.

As well as being co-lead over the full grant, Kuhn heads up one of the grant’s main goals, or cores: that of the structural biology of the antibodies and viruses themselves.  Increasing resolution in microscopes and other tools allows scientists to better see the virus and more rapidly identify possible routes for vaccines and treatments.

“If we take dengue virus, a very important human pathogen that affects up to 400 million people a year, there are certain features on the virus surface that antibodies like to recognize to prevent virus infections,” Kuhn said. “Even if we have an unknown virus of the same group, we can predict where the same type of residues are going to be and computationally design an antibody around that.”

Kuhn’s team uses AI as well as increased abilities to visualize viruses to pinpoint the most effective and efficient routes for vaccines. Just as the resolutions of modern telescopes, like the James Webb Space Telescope, are allowing astronomers to peer ever more deeply and clearly into space, the tools to look at small things are improving. The increased resolution means that rather than guessing, scientists can quickly see and theorize what parts of the virus to target, drastically decreasing the amount of time it takes to address a viral infection.

“We are using the most modern tools and a team of the best experts to understand how the human immune system can be primed and targeted for the fastest, most effective response against viral pathogens,” Kuhn said. “Our primary responsibility is to improve human health in the U.S. and the world.”

This work is part of Purdue’s One Health initiative.

About Purdue University 

Purdue University is a public research institution demonstrating excellence at scale. Ranked among top 10 public universities and with two colleges in the top four in the United States, Purdue discovers and disseminates knowledge with a quality and at a scale second to none. More than 105,000 students study at Purdue across modalities and locations, including nearly 50,000 in person on the West Lafayette campus. Committed to affordability and accessibility, Purdue’s main campus has frozen tuition 13 years in a row. See how Purdue never stops in the persistent pursuit of the next giant leap — including its first comprehensive urban campus in Indianapolis, the Mitch Daniels School of Business, Purdue Computes and the One Health initiative — at https://www.purdue.edu/president/strategic-initiatives

Media contact: Brittany Steff, bsteff@purdue.edu  

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