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In a unique innovation, a group of scientists from the Indian Institute of Science (IISc) Bangalore designed a technology that can stop the entry of coronavirus inside our body. The researchers said, they have developed a new class of artificial peptides or miniproteins that “can not only block virus entry into our cells but also clump virus particles together, reducing their ability to infect." The study has been published in the journal Nature Chemical Biology. 

How did the researchers come up with the technology? 

Noting that protein-protein interaction is often like that of a lock and a key, they said, “interaction can be hampered by a lab-made miniprotein that mimics, competes with, and prevents the 'key' from binding to the 'lock', or vice versa." 

The researchers used the same approach to design miniproteins that can bind and block the spike protein on the surface of the coronavirus, which helps it to enter and infect the human cells. This binding was further characterised extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods.

How do the miniprotiens work?

Miniproteins are helical, hairpin-shaped peptides. They can pair up with another of its kind, forming what is known as a dimer. Each dimeric ‘bundle’ presents two ‘faces’ to interact with two target molecules.

The researchers hypothesised that the two faces would bind to two separate target proteins locking all four in a complex and blocking the targets’ action. "But we needed proof of principle," said Jayanta Chatterjee, Associate Professor in the Molecular Biophysics Unit (MBU), IISc, and the lead author of the study.

So they went on to test it by using SIH-5 miniprotein to target the interaction between the spike protein of COVID virus and ACE2 protein in human cells. 

“When a SIH-5 dimer encountered an S protein, one of its faces bound tightly to one of the three RBDs on the S protein trimer, and the other face bound to an RBD from a different S protein," they said adding, “This ‘cross-linking’ allowed the miniprotein to block both S proteins at the same time."

The spike protein is a complex of three identical polypeptides, each of which contains a Receptor Binding Domain (RBD) that binds to the ACE2 receptor on the host cell surface, facilitating viral entry into the cell.

The SIH-5 miniprotein was designed to block the binding of the RBD to human ACE2.

(With inputs from agencies)

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