Oxford scientists working out of the school's Department of Physics have developed a new type of COVID-19 test that can detect SARS-CoV-2 with a high degree of accuracy, directly in samples taken from patients, using a machine learning-based approach that could help sidestep test supply limitations, and that also offers advantages when it comes to detecting actual virus particles, instead of antibodies or other signs of the presence of the virus which don't necessarily correlate to an active, transmissible case.
According to the study by researchers from the Wroclaw University of Science and Technology and the University of Texas Health Science Center at San Antonio (UT Health San Antonio), the joint efforts of the authors lead to the development of two molecules that impede the function of the so-called "scissor" enzyme known as SARS-CoV-2-PLpro.
The scientists developed the inhibitors, which are very efficient at blocking the activity of SARS-CoV-2-PLpro, yet do not recognise other similar proteins in human cells.
"This enzyme executes a double-whammy".
'It stimulates the release of proteins that are essential for the virus to replicate, and it also inhibits molecules called cytokines and chemokines that signal the immune system to attack the infection, ' Olsen said. "The enzyme acts like a molecular scissor".
The enzyme literally slices human proteins ISG15 and ubiquitin, which stabilize protein integrity.
Dr. Olsen's team, which recently moved to the Long School of Medicine at UT Health San Antonio from the Medical University of SC, solved the three-dimensional structures of SARS-CoV-2-PLpro and the two inhibitor molecules, which are called VIR250 and VIR251.
"A significant concern for the upcoming winter months is the unpredictable effects of co-circulation of SARS-CoV-2 with other seasonal respiratory viruses", she said.
Specificity will be a key determinant of therapeutic value down the road, he said. They learned that SARS-CoV-2-PLpro processes ubiquitin and ISG15 much differently than its SARS-1 counterpart.
By understanding similarities and differences of these enzymes in various coronaviruses, the researchers said it may be possible to develop inhibitors that are effective against multiple viruses.