Inhibiting SARS-CoV-2 Replication

A group of German pharmaceutical chemists discovered 2 families of active substances that can block the replication of the SARS-CoV-2. These substances switch off the key enzyme of the virus, the main protease.

"The main protease is an extremely promising starting point for coronavirus drug research," Christa E. Müller, PhD, Pharmaceutical Institute at the University of Bonn, said. "If this enzyme is blocked, viral replication in the body's cells is stopped."

The findings were reported in the Angewandte Chemie International Edition.

SARS-CoV-2 first has its genome translated from RNA into a large protein strand. The viral main protease then cuts this protein chain into smaller pieces, from which the new virus particles are formed.

These pharmaceutical chemists developed potential inhibitors based on the main protease and the mechanism by which the SARS-CoV-2 replicating enzyme works. They created high-throughput screening, which showed 2 classes of drugs that appeared to be particularly promising.

Customized compounds of both classes were then synthesized. They stuck 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," Müller reports. "They also inhibit a human enzyme that helps the virus enter body cells."

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