Scientists use computer simulations to identify future targets for Covid-19 treatment

University of Warwick scientists model movements of nearly 300 protein structures in Covid-19. Scientists can use the simulations to identify potential targets to test with existing drugs, and even to study efficacy with future Covid modifications.

A simulation of a virus spike protein, part of the virus’s corona, shows a promising mechanism that can be blocked. Researchers have publicly published data about each protein structure to aid in efforts to find drug targets.

Researchers have described a device in a specific Covid-19 corona that could help scientists find new cures for the virus quickly, and quickly test whether existing cures already prone to working with mutated versions as they develop.

The team, led by the University of Warwick as part of the EUTOPIA community of European universities, has simulated trends in nearly 300 Covid-19 virus spike protein protein structures using computer modeling techniques, in an effort to identify promising drug targets. for the virus.

In a new paper published today (February 19) in the magazine Scientific Reports, the team of physicists and life scientists details the techniques they would use to determine the flexibility and dynamics of all 287 protein structures for the Covid-19 virus, also known as SARS -CoV-2, identified so far.

Just like organisms, viruses are made up of proteins, large biomolecules that perform different functions. The scientists believe that one way of treating the virus could be to inhibit the ability of these proteins to move.

They have made their data, films and structural information, detailing how the proteins move and deform, for the 287 protein structures for Covid-19 a were available at the time of the study, publicly accessible to allow others to explore possible avenues for treatment.

The researchers focused specific efforts on a part of the virus called the spike protein, also known as the Covid-19 echo land structure, which is the expanded corona that gives coronaviruses its name.

It is this spike that allows the virus to attach itself to the enzyme ACE2 in the human cell membrane, through which it causes Covid-19 signals.

The spike protein is actually a homotrimer or three of the same type of protein combined. By shaping the movements of the proteins in the spike, the researchers identified a ‘hinged’ mechanism that allows the spike to slide on a cell, while also opening a tunnel in the virus that is prone to delivery of the disease to the hook. cells.

The scientists suggest that by finding a suitable molecule to block the apparatus – literally, by inserting a molecule of appropriate size and shape – it will be possible for pharmaceutical scientists quickly identify drugs that may be effective against the virus.

Lead author Professor Rudolf Roemer from the Department of Physics at the University of Warwick, who carried out the work while on Sunday leave at CY Cergy-Paris Université, said: “Knowing how the equipment is this works one way in which you can stop the virus, and in our study, we are the first to see the exact movement of the opening. Now that you know what the scope of this movement is, you can find out what can be blocked.

“All those interested in exploring whether the protein structures in the virus could be drug targets should be able to study this and see if the dynamics we are experiencing. useful count for them.

We were only able to take a closer look at all the 287 proteins in the time available. People should use the movement we are seeing as a starting point for their own development of drug targets. If you find an interesting trend for a particular protein structure in our data, you can use that as a basis for further modeling or experimental studies. “

Rudolf Roemer, Principal study author and Professor, Department of Physics, University of Warwick

To study protein movements, the scientists used a protein flexibility modeling method. This involves reconstructing the structure of the protein as a computer model and then simulating how that structure was moved by treating the protein as a material made up of a hard and elastic substrate, with a possible movement of these substrates defined by chemical bonds.

The method has been shown to be particularly effective and correct when applied to major proteins such as coronary virus spike proteins. This can allow scientists to quickly identify promising drug targets for further study.

The protein structures on which the researchers based their modeling are all available in the Protein Data Bank. Anyone who publishes a biological structure needs to add it to the protein database so that it is freely available in a standard format for others to download and explore further.

Since the Covid-19 pandemic began, scientists around the world have submitted thousands of Covid-19-related protein structures to the Protein Data Bank.

Dr Roemer said: “The gold standard in computer modeling of protein dynamics is a method called molecular dynamics. Unfortunately, this method can be very time consuming especially for proteins. large ones like the Covid-19 spike, which has nearly 3000 residues – the basic building block of all proteins.Our method is much faster, but naturally we have to make harder simplification assumptions. that is, we can make structures that are much larger than other methods are possible.

“At this time, no one has published tests identifying protein crystal structures for the new variants of Covid-19. If new structures come out for the mutations in the virus, carriers could -science to quickly test existing treatments and see if the new mechanics have affected their effectiveness using our method. “