UC Irvine scientists get ‘initial hit’ in developing drug to treat COVID-19

On August 3, 2020, bioRxiv published an article titled, “Structure-Based Design of a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease” which describes University of California, Irvine professor James Nowick’s development of a ring-shaped molecule called a macrocycle. Macrocycle’s are designed to gum up the machinery of the COVID-19 virus by blocking the action of an enzyme essential for it to reproduce.

Adam Kreutzer, a project scientist in Nowick’s group, spearheaded the effort to design and produce the new molecule. “We didn’t know for sure if we could synthesize the macrocycle, because sometimes macrocycles can be difficult to synthesize,” Nowick said.

But Kreutzer succeeded on his first try with the macrocycle the team thought might work. “It’s a novel molecule that’s never been made before,” he said.

The researchers then tested the macrocycle to see if it could block the action of the coronavirus enzyme. The macrocycle binds to an enzyme molecule called the main protease that’s necessary for the virus to function. The protease cleaves long strings of proteins that the virus forces its host cell to make into separate components, which the virus then uses to keep replicating.

The new macrocycle, Kreutzer said, “sits there in the active site of the enzyme and makes it nonfunctional.”

Now that Nowick’s lab has a prototype called an “initial hit,” researchers need to make additional molecules that are more effective in blocking the protease. Then they must figure out how to actually deliver the best molecule to infected cells.

This means that, while the new macrocycle is a promising first step, Nowick said, “people need to understand that it’s a long way from a drug candidate.”

You can read the full article here!