Solving Molecular Mechanics of RNA Viruses
What all started as a way to make some work study money during college, quickly turned into a life-long passion for Professor Olve Peersen. Peersen, who originally went to college to become an engineer, found his passion for molecular and structural biology while working as an undergraduate researcher in a lab. Now, decades later, Peersen has dedicated his work to building a deep understanding of the molecular mechanisms that allow viruses to replicate and infect humans and animals.
Peersen’s lab studies a wide variety of related viruses including picornaviruses like poliovirus and coxsackievirus, coronaviruses, and HIV. In the early 2000s, Peersen focused on solving the molecular structures of their polymerases to understand how these RNA viruses replicate.
“After a few years, we finally got a structure where we could catch the RNA genome replication in action,” said Peersen. “That was not only a big breakthrough for the lab, but for the field as a whole.”
Peersen found that compared to most other polymerases, these viral ones have a more compact structure and only subtle internal movements during the replication reaction. This discovery explains why some antiviral medications are not very effective. Antivirals are deployed in the body to inhibit the molecular mechanisms the virus needs to copy itself, however, it’s difficult to target these tiny structures and movements with modern medicine.
In 2020, Peersen was on sabbatical in France when the COVID-19 pandemic began. COVID-19 is caused by the SARS-CoV-2 virus, and the lab he was in had already studied the related SARS-CoV-1 virus that appeared in 2002. Because Peersen was deeply familiar with viral polymerases, he was able to quickly contribute his expertise to research on this new emerging virus.
“It was really nice to be able to have 15 years of basic research understanding in my head and then use that knowledge to immediately pivot into being useful for interpreting what was going on.”
Peersen’s work on COVID-19 resulted in multiple peer-reviewed papers that added to the robust scientific knowledge of coronaviruses. As it turns out, the core of the SARS-CoV-2 polymerase is very similar to the poliovirus polymerase, but it replicates RNA four times faster.
Peersen’s prolific research program has been recognized through the awarding of a National Institutes of Health MERIT grant in 2023 that will fund his work for the next ten years. In the future, Peersen plans to use cryo-electron microscopy, a technology that uses electrons to determine 3D structures of biomolecules, to further his research into virus replication.
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