Recently, scientists from MIT and other institutions have designed a novel peptide using computer models of protein interactions that bind to coronavirus proteins and break them down through cellular pathways, and this type of peptide could serve as a potential therapy to inhibit SARS-COV-2 virus replication in infected cells.
The idea is to use a computer technique to engineer peptides to treat COVID-19, and once they get into cells, they can simply tag and degrade the virus.
Now that the new peptide has been tested in human cells, the researchers are planning cell and animal studies to assess its efficacy, and report their preliminary findings on June 1st on bioRxiv, a preprint platform.
Scientists are looking at a number of different strategies to develop novel therapies for COVID-19. One area of interest is developing specific antibodies to bind to inactivated viral proteins such as spikes, which coronavirus USES to enter human cells;
One way to do this is to replace antibodies with small fragments of proteins called peptides;
MIT researchers are working on engineering of peptide modified to strong combination to the spike protein within the cell, also can use these polypeptides stimulate cell broken viral protein, the researchers of idea is to make the polypeptide recruit called E3 ubiquitin ligase of naturally occurring proteins when the cell no longer needs the protein, it can be marked for destruction.
In order to develop can spike protein peptide, the researchers used protein interactions, a computer model, the model after can optimize the bonding strength between the two kinds of protein, the researchers Chatterjee and others similar computer methods recently used to design for the improvement of gene editing version of the enzymes, the new CRISPR – Cas9 enzymes can be targeted more than 70% of the DNA sequence, and the most common CRISPR – Cas9 can only reach about 10%.
In this case, the researchers used the human ACE2 protein, which exists on the surface of specific human cells and binds to coronavirus spike proteins, as a starting point.
Researchers using the developed model will ACE2 protein is broken into many small pieces, then through calculation to predict these fragments may interact with spike protein, they guide the model to optimize the three characteristics, first of all, the engineering modification of peptide has given it to spike protein has the strong affinity, secondly, these peptides can also with other coronavirus spike protein, perhaps can effectively resist the past or the future of other coronavirus strain, third, the researchers said that these peptides are not strong combination with human proteins – to the protein,
Under normal circumstances, integrins bind to ACE2 receptors in the body.
This process produces about 25 candidate peptides that can be fused with the E3 ubiquitin ligase and tested in human cells that express spikes (receptor-binding domains, or RBD).
The researchers finally identified a candidate peptide called 23 amino acid peptides that break down about 20 percent of RBD proteins in cells. However, this peptide is not as effective as ACE2, which breaks down about 30 percent of RBD proteins.
To improve the peptide’s performance, the researchers used the model to simulate how RBD binding would be affected if different amino acids were replaced at 23 locations, an optimization that resulted in a mutant peptide that increased the degradation rate to more than 50%.
Mark is broken
A key advantage of this peptide is its small size. Even when fused with the E3 ubiquitin ligase, the entire strand is only about 200 amino acids in length.
Another possibility is to transport peptides that bind to the coronavirus’s spike proteins and carry the virus inside the host cell, in which case the virus is labeled and destroyed as soon as it enters the cell.
Now researchers plan in SARS – CoV – 2 virus testing the new peptide in human cells, if these tests are successful, researchers hope to be able to test of the peptides in animal models, the next step they will continue to further study to improve the peptides to make it better able to combine with the spike protein and play a role.