IISc scientists report miniproteins that can fight COVID-19

The Indian Institute of Science (IISc) has reported that a new class of artificial peptides or miniproteins (molecules) that help fight COVID-19 rendering viruses inactive. While blocking the entry of certain viruses into the cells, they will also clump the virus particles together to reduce the infection levels.

While the Hammers have shown good results, the researchers are planning to bring out anti-viral drugs that can hopefully fight for COVID-19 and also for further testing in the field of oncology.

Speaking to The HinduJayanta Chatterjee, Associate Professor in the Molecular Biophysics Unit, IISc and also the lead author of the study, published in Nature Chemical Biologyexplained the mechanism in layman terms thus:

“Typically, a drug molecule binds to one protein and in most cases, they stay attached for some time, and then dissociate together. These miniproteins are helical, hairpin-shaped peptides, each capable of pairing with another of its kind, forming what is known as a dimer. These bundles have two identical faces bound by high affinity. It is extremely difficult to denature them and when they bind to the target, they also dimerise these targets. This allows one to develop an entirely new mechanism of the drugs. ”

He further stated, “The part which is involved in binding to the cells is nullified. So instead of attaching the virus to the cell and going inside, the viruses clump together. This is not something that antibodies can often do ”. He added that this could help many viruses and could also help in the field of oncology where there is no rapid mutation. The team has applied for a patent.

During the study, a new approach wherein miniprotiens can bind to and block the protein spike of the SARS-CoV-2 virus, was explored by scientists. To test their hypothesis, they used a miniprotein called SIH – 5 to target the interaction between the spike (S) protein of the virus and ACE2 protein in human cells.

“The S protein is a trimer – a complex of three identical polypeptides. Each polypeptide contains a receptor binding domain (RBD) that binds to the ACE2 receptor on the host cell surface. This interaction facilitates viral entry into the cell, ”said a press release from IISc.

“The SIH-5 miniprotein was designed to block the binding of RBD to human ACE2. When a SIH-5 dimer encounters an S protein, one of its faces bound tightly to three RBDs on one S protein trimer, and the other face bound to an RBD from a different S protein. This ‘cross-linking’ allowed the miniprotein to block both S proteins at the same time, ”the release further said.

To test effect of SIH – 5 on COVID-19, when the hamsters were administered to miniproteins and exposed to the virus at the Lab of Raghavan Varadarajan, Professor, Molecular Biology Unit of IISc, it was observed that there was no weight loss, reduced viral load and lesser lung damage.

“We are planning on talking to pharmaceutical companies and possibly conducting clinical trials before releasing human beings,” said Somnath Dutta, assistant professor at MBU and one of the study’s affiliated authors.