Miniproteins to render SARS-Cov-2 inactive

BENGALURU: While emergence of new strains of Covid-19 has diminished the protection offered by vaccines, researchers at the Indian Institute of Science (IISc) now have developed an alternative mechanism to render viruses like SARS-CoV-2 inactive.

In a study published in Nature Chemical Biology, the researchers report the design of a new class of artificial peptides or miniproteins that can not only block virus entry into our cells but also clump virions (virus particles) together, reducing their ability to infect.

According to a release, a protein-protein interaction is often like that of a lock and a key. This 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 team has exploited this approach to design miniproteins that can bind to, and block the spike protein on the surface of the SARS-CoV-2 virus.

This binding was further characterised extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods.These miniproteins 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. 

The researchers decided to test their hypothesis by using one of the miniproteins called SIH-5 to target the interaction between the spike (S) protein of SARS COV2 and ACE 2 protein in human cells. The next step, according to Jayanta Chatterjee, Associate Professor in the Molecular Biophysics Unit, IISc, and the lead author of the study was to ask if SIH 5 would be useful for preventing Covid-19 infection. The team first tested the miniprotein for toxicity in mammalian cells in the lab and found it to be safe.