Molecular technology could provide key to drug discovery against SARS-CoV-2

Researchers are using a new method to isolate the complex between SARS-CoV-2 and the ACE2 receptor to keep it integrated into the cell membrane.


Researchers are working to isolate and extract the COVID-19 encounter complex in a sufficiently stable form for the identification of target sites for future antiviral drugs against SARS-CoV-2. The study is being conducted at the University of Birmingham, UK.

The encounter complex is formed when the SARS-CoV-2 Spike (S) protein locks to a binding site on an angiotensin converting enzyme (ACE2) receptor, which is a complex protein integrated into cell membranes of the lungs and cells that line the nose. and the respiratory tract.

Although it was first isolated last year, the team said the methods used involved complete extraction of ACE2 receptors from cell membranes. This removal of the membrane support structure affects the stability of the receptor, making it difficult to study its structure and function.

In their study, the researchers used molecular “ cookie cutters ” made from polymers to isolate the complex and keep it integrated into the cell membrane, preserving the complete structure of the molecule in its original context and under a stable shape. The polymers are called styrene maleic anhydrides (SMA) and the resulting structure is known as the SMA lipid particle (SMALP) because it includes lipids from cell membranes.

Researchers believe this is the very first COVID-19 encounter complex with an intact membrane. This first project also aims to characterize the complex with a view to publishing its structure.

Dr Bart Verbraeken, director of the Orbiscope business unit, which provided the SMAs used in the study, said: “Beyond COVID-19, we believe that SMAs have enormous potential to unlock restrictions in the study. the drug pipeline, enabling studies of receptors in their native environments will define drug targets more precisely than ever before. “