Chennai: In an important first step towards building a comprehensive 3D model of the enzymatic protein, scientists have performed the first room-temperature X-ray measurements on the SARS-CoV-2 main protease.
Made by a team of researchers at the Department of Energy’s Oak Ridge and Argonne national laboratories (ORNL), the model will be used to advance supercomputing simulations aimed at finding drug inhibitors to block the virus’s replication mechanism and help end the Covid-19 pandemic. Their research results are publicly available and have been published in the journal Nature Communications.
ORNL’s Andrey Kovalevsky, corresponding author, said, “The protease is indispensable for the virus life-cycle. The protein is shaped like a valentine’s heart, but it really is the heart of the virus that allows it to replicate and spread. If you inhibit the protease and stop the heart, the virus cannot produce the proteins that are essential for its replication. That’s why the protease is considered such an important drug target.”
While the structure is known from cryogenically preserved crystals, “This is the first time the structure of this enzyme has been measured at room temperature, which is significant because it’s near the physiological temperature where the cells operate.”
SARS-CoV-2, the virus that causes the disease Covid-19, reproduces by expressing long chains of proteins that must be cut into smaller lengths by the protease enzyme.
Protease is a type of enzyme that breaks down proteins into smaller proteins or smaller protein units, such as peptides or amino acids. HIV protease cuts up large precursor proteins into smaller proteins.
ORNL’s Daniel Kneller, the study’s first author, said, “growing protein crystals and collecting data is a tedious and time-consuming process. In the time it typically takes to prepare and ship the sample to a synchrotron, we were able to grow the crystals, take the measurements and begin analysing the data.”
He added: “And, when there’s a pandemic with many scientists mobilising to study this problem, there’s not a day to spare.”