On April 3, as COVID-19 was already rapidly spreading across the US, the National Science Foundation issued a call for immediately implementable research to fight the disease as part of CARES - the federal Coronavirus Aid, Relief and Economic Security Act.
Within a week, University of Virginia associate professor of chemical engineering Bryan Berger and his longtime collaborator, Jeffery Klauda, responded.
Berger and Klauda, an associate professor in the Department of Chemical and Biomolecular Engineering at the University of Maryland, proposed combining the power of mathematical modeling with high-throughput screening to fast-track answers crucial to understanding how SARS-CoV-2, the coronavirus that causes COVID-19, propagates within its human host. High-throughput methods automate experiments to increase the number that can be performed and speed the time to discovery.
Berger and Klauda each received a $150,000 award from EAGER, the National Science Foundation's Early Concepts Grant for Exploratory Research funding program, which is designed for "untested, but potentially transformative" research approaches. The grants will support Berger and Klauda's study of proteins linked to the virulence of SARS-CoV-2 in humans using integrated experimental and computational methods.
The viral proteins Berger and Klauda study, named ORF7a and ORF7b, form larger protein complexes unique to coronaviruses. Such protein structures come together through a chemical process called oligomerization. Berger likened the formation of these complexes to organizing a parade.
"One person (or protein) alone can't make a parade, but once groups of people (or proteins) assemble in a specific order you have a celebration. Depending on the order, you can have a great (effective) parade or one that's not as good (effective)," Berger said.
"There is evidence these complexes are important in preventing proper host immune recognition and response," Berger said. "ORF7a and ORF7b are not well understood, but previous studies suggest they are key for rapid spread during infection - i.e., they dampen the individual's immune response, so the virus can propagate more quickly once an infection occurs."