Indian scientists develop peptides that arrest coronavirus entry into human cells

Indian scientists have designed a new class of synthetic peptides that can potentially block the entry of SARS-CoV-2 virus into human cells.

The peptides have the capability to clump the COVID-19 virions (virus particles) together, thus reducing their ability to infect the cell.

The development comes at a time when periodic outbreaks of COVID-19 are being reported in several parts of the country, raising fears of re-imposition of some old restrictions observed during the two consecutive lockdowns of 2020 and 2021.

At a time when India’s vaccination programme is all set to touch the 200 crore mark, this novel approach promises an alternative mechanism to render viruses like SARS-CoV-2 inactive, providing a new class of peptides as antivirals.

Besides, the rapid emergence of new strains of coronavirus has the potential to diminish the protection offered by COVID-19 vaccines, calling for new approaches to prevent infection by the virus.

In view of the need to boost immune protection, the Modi government has announced free booster shots for everyone above the age of 18 for 75 days. A wide section of this category has already received two doses of the vaccine.

How do synthetic peptides work?

It is known that protein-protein interaction is often like that of a lock and key. This interaction can be hampered by a synthetic peptide that mimics, competes with, and prevents the ‘key’ from binding to the ‘lock’, or vice versa. The newly designed synthetic peptides will work on the same principle.

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Scientists at the Indian Institute of Science (IISc), in collaboration with researchers from the CSIR-Institute of Microbial Technology, have used this approach to design peptides that can bind to and block the spike protein on the surface of SARS-CoV-2 virus, stated the Ministry of Science & Technology.

“The designed peptides are helical, hairpin-shaped, 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. In the study published in Nature Chemical Biology, the researchers hypothesised that the two faces would bind to two separate target proteins locking all four in a complex and blocking the targets’ action,” the statement read.

The path-breaking research was supported under the COVID-19 IRPHA (Intensification of Research in High Priority Area) cell of the Science and Engineering Research Board (SERB), a statutory body of the Department of Science and Technology (DST), the statement added.

The Indian scientists working on the project decided to test their hypothesis by using a peptide called SIH-5 to target the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein, the SARS-CoV-2 receptor in human cells.

When hamsters were dosed with the peptide and subsequently exposed to a high dose of SARS-CoV-2, they showed decreased viral load and less cell damage in the lungs compared to hamsters exposed only to the virus, demonstrating the ability of peptides to act as antivirals.

“The SIH-5 peptide 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 SIH-5 to block both S proteins at the same time. Under cryo-EM, the S proteins targeted by SIH-5 appeared to be attached head-to-head, and the spike proteins were being forced to form dimers. Subsequently, the researchers showed that SIH-5 inactivated the viruses efficiently by cross-linking the spike proteins from different virus particles,” the Ministry of Science & Technology statement said.

The team of Indian researchers believe that with minor modifications and peptide engineering, this lab-made mini protein could inhibit other protein-protein interactions as well.

The path-breaking research was supported under the COVID-19 IRPHA (Intensification of Research in High Priority Area) cell of the Science and Engineering Research Board (SERB), a statutory body of the Department of Science and Technology (DST), the statement added.

The findings of Indian scientists have been published in Nature magazine.

Further studies are underway and the next stages of development will hopefully provide a new way of protection from COVID-19, in addition to the existing systems of treatment and vaccination, say scientists.