IISC scientists develop miniproteins that may prevent COVID infection

Researchers at the Indian Institute of Science (IISc) Bangalore have designed a new class of artificial peptides or miniproteins that they say can render viruses like SARS-CoV-2 inactive.

Mini-protein:

• The mini proteins can not only block virus entry into our cells but also clump virus particles together, reducing their ability to infect.
• The researchers noted that a protein-protein interaction is often like that of a lock and a key.
• This interaction can be hampered by a lab-made mini protein that mimics, competes with, and prevents the 'key' from binding to the 'lock', or vice versa.

Characteristics of a mini-protein:

• These mini proteins are helical, hairpin-shaped peptides, each capable of pairing 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.

About the research:

• The team designed mini proteins that can bind to, and block the spike protein on the surface of the SARS-CoV-2 virus, which helps it to enter and infect the human cells.
• Using one of the mini proteins called SIH-5 to target the interaction between the spike protein of SARS-CoV-2 and ACE2 protein in human cells.
• 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 mini protein was designed to block the binding of the RBD to human ACE2.
• 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.
• This ‘cross-linking’ allowed the mini protein to block both S proteins at the same time.