Indian researchers developed novel method to render SARS-CoV-2 inactive

New synthetic peptides that can both prevent the SARS-CoV-2 virus from entering cells and clump the virus particles together to lessen their capacity to infect living cells have been created by Indian scientists.With the help of this innovative technique, viruses like SARS-CoV-2 can be rendered dormant, opening the door for a new family of peptide antivirals.

Key Points:

• According to the Ministry of Science and Technology, scientists from the Indian Institute of Science (IISc) and the CSIR-Institute of Microbial Technology have created a novel mechanism to inactivate the COVID (SARS-CoV-2) virus by preventing its entry into cells and lowering its capacity to infect people.
• The COVID-19 vaccines’ effectiveness against the SARS-CoV-2 virus has been reduced by the quick emergence of new strains, necessitating the development of fresh methods for preventing virus infection.
• These peptides were created by scientists from the Indian Institute of Science working with specialists from the CSIR-Institute of Microbial Technology.
• With the use of cryo-electron microscopy (cryo-EM) and other biophysical techniques, this binding was further and thoroughly characterised.

About the Research:

• The study was funded by the Department of Science and Technology’s Department of Engineering and Research Board, a governmental authority, through the COVID-19 IRPHA call.
• The created peptides have helical, hairpin-like shapes and are each capable of producing a dimer by joining forces with another of their sort. Two “faces” are presented by each dimeric “bundle” to interact with two target molecules.
• The researchers in the study that was published in Nature Chemical Biology postulated that the two faces would attach to two different target proteins, trapping all four of them in a complex and inhibiting the function of the targets.
• The scientists made the decision to test their theory by focusing on the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein, the SARS-CoV-2 receptor in human cells, using a peptide named SIH-5.
• A compound made up of three identical polypeptides, the S protein is a trimer. A Receptor Binding Domain (RBD) found in each polypeptide interacts to the ACE2 receptor on the surface of the host cell.
• Viral entrance into the cell is facilitated by this contact.

Purpose of SIH-5:

• The SIH-5 peptide was created to prevent the RBD from attaching to human ACE2. One face of a SIH-5 dimer strongly linked to one of the three RBDs on a S protein trimer, and the other face bound to an RBD from a different S protein when it came into contact with a S protein.
• The SIH-5 was able to inhibit both S proteins simultaneously thanks to this ‘cross-linking’.
• The SIH-5-targeted S proteins looked to be linked directly to one another under cryo-EM, while the spike proteins were being compelled to form dimers.
• The scientists next demonstrated that SIH-5 effectively inactivated the viruses by cross-linking the spike proteins from several virus particles.

The peptide was examined for toxicity in mammalian cells in the laboratory by a team made up of scientists from IISc and the CSIR-Institute of Microbial Technology, and it was confirmed to be safe. This class of peptides shows potential as antivirals since after receiving the peptide dose, hamsters subjected to a high dose of SARS-CoV-2 showed reduced viral load and significantly less lung cell damage than hamsters exposed simply to the virus.