"By unlocking the three-dimensional structure of this enzyme – known as papain-like-protease (PLpro) – we now have a molecular road map to design new drugs that could potentially treat SARS-infected patients, or perhaps patients suffering from other SARS-related illnesses such as the common cold, bronchitis or pneumonia," said Andrew Mesecar, associate professor of pharmaceutical biotechnology in the UIC College of Pharmacy. "We are attempting to use the same approach that has been accomplished in designing effective drugs against HIV protease, which has led to the development of new drugs to fight the AIDS virus."
Mesecar said that the knowledge gained from this new atomic structure has the potential to go beyond the treatment of patients infected with the coronavirus that causes SARS.
The papain-like-protease enzyme is essential for viral replication and infection of all of the coronaviruses involved in upper respiratory infections. Eliminating the enzyme should stop the infection, Mesecar said.
During the UIC study, graduate student Kiira Ratia used X-ray crystallography, a technique that involves bombarding a crystalline form of the enzyme with an intense beam of X-rays that are bent by atoms in the molecules to unlock the details of the molecular structure.
As the X-rays leave the crystal, a unique pattern is created on an ultra-high resolution charge-coupled device camera, a sensor for recording images often used in digital photography and astronomy. The images were then interpreted by computer to reconstruct the positions of all the component atoms.
"We have already discovered compounds that can bind to these pockets and inhibit the activity of this enzyme," Mesecar said. "We have made remarkable progress in a short period of time in generating lead drug-like compounds against the enzyme."
MEDICA.de; Source: University of Illinois at Chicago