Researchers at the Indian Institute of Science (IISc) in Bangalore have made a new type of mini proteins, or artificial peptides that they say can stop viruses like SARS-CoV-2 from working. Nature Chemical Biology, a magazine, wrote about the study. Researchers looked to see if it was dangerous to mammalian cells and found that it wasn’t.
Key Highlight:
- IISc Bangalore researchers have designed artificial peptides or mini proteins that can inactivate viruses like SARS-CoV-2.
- The team used this strategy to build mini proteins that attach to and disrupt the SARS-CoV-2 virus’s spike protein, which helps it infect human cells.
- The mini protein is ‘cross-linked’ to inhibit both S proteins.
- Under cryo-EM, the SIH-5-targeted S proteins showed head-to-head.
- Miniprotein is stable at room temperature for months.
Researchers at the Indian Institute of Science (IISc) in Bangalore have made a new type of mini proteins, or artificial peptides that they say can stop viruses like SARS-CoV-2 from working. The study, published in the journal Nature Chemical Biology, says that the mini proteins can stop viruses from getting into our cells and stick virus particles together, making it harder for them to spread disease.
Researchers at the Indian Institute of Science (IISc) in Bangalore have made a new type of mini proteins or artificial peptides that can stop viruses like SARS-CoV-2 from working. The study, published in the journal Nature Chemical Biology, says that the mini proteins can stop viruses from getting into our cells and stick virus particles together, making it harder to spread disease.
The researchers said that the relationship between two proteins is often like a lock and a key.
They said that a lab-made mini protein can slow down this interaction that acts like the “key,” competes with it, and stops it from binding to the “lock.”
The team used this method to make mini proteins that can bind to and block the SARS-CoV-2 virus’s spike protein, which helps it get into human cells and infect them.
Cryo-electron microscopy (cryo-EM) and other biophysical methods were used to learn more about this binding.
These mini proteins are made up of peptides in the shape of a helical hairpin. Each peptide can pair up with another of its kind to make what is called a dimer. Each “bundle” of two dimeric molecules has two “faces” that can interact with two different target molecules.
The researchers thought that the two faces would bind to two different target proteins, putting all four in a complex that would stop the targets from doing what they were supposed to do.
“But we needed proof of principle,” said Jayanta Chatterjee, the study’s lead author and an associate professor in the Molecular Biophysics Unit (MBU) at IISc.
The team decided to test their theory by using one of the mini proteins called SIH-5 to target the interaction between the spike protein of SARS-CoV-2 and the ACE2 protein in human cells.
The spike protein is a group of three identical polypeptides. Each polypeptide has a Receptor Binding Domain (RBD) that binds to the ACE2 receptor on the host cell’s surface, making it easier for the virus to get inside the cell.
The SIH-5 mini protein was made to stop the RBD from binding to ACE2 in humans.
When a SIH-5 dimer met a S protein, one of its faces was tightly attached to one of the three RBDs on the S protein trimer, and the other face was attached to an RBD from a different S protein.
This “cross-linking” allowed the mini protein to stop both S proteins at once.
“Several monomers can stop their targets from moving. (But) cross-linking of S proteins stops them from working better, “said Chatterjee.
Researchers said that when cryo-EM was used, the S proteins that SIH-5 was looking for seemed to be attached head-to-head.
“We thought we would see one spike trimer bound to SIH-5 peptides. I saw a building that was much longer, “Somnath Dutta, an assistant professor at MBU and one of the study’s co-authors, said.
Dutta and others noticed that the spike proteins were forced to form dimers and clumped with the mini protein.
This kind of clumping can make multiple spike proteins of the same virus inactive simultaneously, as well as multiple virus particles.
Also, the mini protein was stable at room temperature for months without getting worse.
To see if SIH-5 could help stop COVID-19 infections, the team first tested the miniprotein’s safety in mammalian cells and found that it was safe.
Then, in the lab of Raghavan Varadarajan, a professor at MBU, the mini protein was given to hamsters, and they were then exposed to SARS-CoV-2.
Compared to hamsters that only got the virus, these animals didn’t lose weight and had a lot less virus in their bodies and much less cell damage in their lungs.
The researchers said that this lab-made mini protein could stop other protein-protein interactions as well with a few small changes and peptide engineering.
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