A team of Purdue University researchers is creating molecules designed to shut down the Middle East respiratory syndrome coronavirus, or MERS-CoV, that recently arrived in the United States.
The virus was confirmed in a U.S. traveler Friday who on April 24 flew from Riyadh, Saudi Arabia, to London, to Chicago and then traveled by bus to Indiana, according to the Centers for Disease Control and Prevention.
There is currently no treatment or vaccine for the virus, which has an estimated fatality rate of 30 percent, said Andrew Mesecar, the Walther Professor of Cancer Structural Biology and a Purdue professor of biological sciences and chemistry who leads the team.
"We are creating molecules to block a key enzyme that allows the virus the live," Mesecar said. "This enzyme has a big mouth that, in a way, allows it to chew up other proteins the virus needs to live. How do we stop a big mouth from chewing things up? We stuff it full of something else. That is what the molecules we invent do. If you can shut down this critical enzyme, you can effectively shut down the virus."
Mesecar and Arun Ghosh, the Ian P. Rothwell Distinguished Professor of Chemistry and Medicinal Chemistry and Molecular Pharmacology at Purdue are creating and testing molecular compounds that could lead to potential treatments for the virus.
Their work began soon after MERS was discovered, and the team, including graduate students Heather Osswald, Sakshi Tomar and postdoctorate students Yahira Baez and Sarah St. John, built on their earlier work to create compounds to stop the SARS virus, which also belongs to the coronavirus family. The team's SARS work paved the way for them to swiftly turn their attention to MERS, reducing parts of the process that would normally take years to a matter of months. They screened compounds they created to block SARS to see if any worked against MERS, Mesecar said.
"Once we found molecules and compounds that showed signs of being effective, we dug in and began manipulating and enhancing them to see if we could invent new molecules that would be more effective and better able to stop the virus," he said. "For a molecule to work and shut down the virus it has to perfectly fit with the target enzyme. The enzyme is like a glove and we have some hands that might fit, but some have fingers that are too long or thumbs that are too big. So, we have to change the fingers and thumbs and create a hand that perfectly fits the glove."
The Purdue research team is well equipped with expertise critical to custom design such drug molecules effective against MERS, Ghosh said.
The MERS virus can spread from ill people to others through close contact, but has not been shown to spread within communities, according to the CDC. MERS causes severe respiratory illness, and symptoms include a fever, cough and shortness of breath. Until now the virus had been mostly confined to the Middle East, but cases had been identified in Britain, France and Italy. In 2013 the head of the World Health Organization called it "a threat to the entire world."
Source: Purdue University