The scientists at Indian Institute of Science (IISc) have reported a new class of artificial peptides or miniproteins (molecules) that will help fight COVID-19 by 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 trials on hamsters have shown good results, the researchers are planning to bring out anti-viral drugs that can hopefully fight COVID-19 and also test for applications in the field of oncology further.
Speaking to The Hindu, Jayanta Chatterjee, Associate Professor in the Molecular Biophysics Unit, IISc and also the lead author of the study, published in Nature Chemical Biology, explained 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 which are helical, hairpin-shaped peptides, each capable of pairing up 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 a completely new mechanism of the drugs.”
He further said, “The part which is engaged in binding to the cells is nullified. So instead of the virus attaching to the cell and going inside, the viruses clump together. This is not something that antibodies typically do”. He added that this could help against several viruses and could also help in the field of oncology where there is no rapid mutation. The team has applied for a patent currently.
During the study, a new approach wherein miniprotiens can bind to and block the protein spike on the surface of SARS-CoV-2 virus, was explored by the 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 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 miniprotein to block both S proteins at the same time,” the release further said.
To test effect of SIH – 5 on COVID-19, when hamsters were administered the 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 maybe conduct clinical trials on human beings before releasing it as an antiviral drug”, said Somnath Dutta, Assistant Professor at MBU and one of the corresponding authors of the study.
