Compounds inhibiting main protease of COVID-19 discovered

A research team at the University of Bonn, Germany, has used high-throughput screening to discover two families of active substances that can block the replication of the SARS-CoV-2 coronavirus.

According to the researchers, these drug candidates are able to switch off the key enzyme of the virus, the so-called main protease. 

The study, published in the journal Angewandte Chemie, stated that the novel coronavirus relies on the main protease as a key enzyme.

"The main protease is an extremely promising starting point for coronavirus drug research," said Professor Christa Müller, one of the lead researchers. "If this enzyme is blocked, viral replication in the body’s cells is stopped."

"A suitable inhibitor must bind sufficiently tightly to the main protease to be able to block its active site," says Prof. Dr. Michael Gütschow, who heads an independent research group on such inhibitors at the Pharmaceutical Institute of the University of Bonn.

The researchers’ high-throughput screening showed two classes of drugs that seemed to be particularly promising. Customised compounds of both classes were then newly synthesised.

These drugs stick to the main protease like chewing gum and block the crucial catalytic center, which prevents the main protease from preparing the virus replication.

"Some of the compounds even have another effect. They also inhibit a human enzyme that helps the virus enter body cells," Müller reported.

"Only through great collaboration have we been able to design, synthesize and biochemically characterize suitable drug candidates," said Gütschow.

"The best compounds represent promising lead structures for drug development," according to Müller.

The team emphasizes that extensive clinical trials have yet to prove whether these candidates also inhibit SARS-CoV-2 replication in humans.