Indian Institute of Science can help protect us from covid-19


It has gained insight into the coronavirus which will help scientists build better defence mechanisms

A group of scientists from the Indian Institute of Science (IISc) have found new insights into the structure of SARS-CoV-2 spike protein which causes covid-19. This new research is significant because it could help in developing treatments against the virus, including vaccines that target spike protein.

But first, what is spike protein? Viruses belonging to the coronavirus family have sharp bumps or fringes on their surface and these are called spike proteins. When seen under a microscope, these spikes look like a fringe or a crown (in Latin, corona means crown). These spike proteins attach the virus to a cell and this helps it gain entry into the cell.

The research on the structure of the spike protein is supported by Departments of Science and Technology and Biotechnology, comprising a group of scientists led by Somnath Dutta who have recently unravelled the spike protein present on the surface of SARS-CoV2.

These spikes are well known for forming the first point of contact with the ubiquitously present hACE2 receptor protein of our cells.

Dutta and his team solved 11 high-resolution structures of covid-19 spike between July 2020 and October 2020, deploying the cryo-electron microscopy (cryo-EM), which is a National cryo-EM facility at IISc.

The study designed at and near physiological pH (pH 6.5, 7.4 and 8.0) enabled the researchers to obtain a reliable picture of the behaviour of the spike protein within the human body that facilitates viral entry into the cells and the downstream disease onset.

“In this first SARS-CoV2 spike protein structure from India, our group showed that there is a preponderance of the “ON” ( 1-Receptor Binding Domain Up) state of spike protein while on either side of the body’s usual pH, the spike assumes an “OFF” ( 3-Receptor Binding Domain Down) state which is unable to attack the cells of our body. This explains why it was easy for the virus to become a pandemic as the natural state of the body offers habitable conditions to the virus. The study also showed that the spike protein is highly flexible and there are myriad structural phases of this protein within each “ON” or “OFF” state,” Dutta

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said.

The team added that although most current vaccines targeted against spike protein show adequate effect against the original and current mutant variants of covid-19, taking into account the knowledge of the intrinsic structural flexibility of the hACE2 recognising region may help in informing the development of broadly neutralizing antibodies (bNAbs) and drug candidates which could be more potent in combating the deadly virus with higher efficiency.

“According to the WHO database, most current vaccines that use whole or part of the spike protein to elicit the production of protective proteins (antibodies) in our bodies, have been seen to be adequately active against both the original strain and the mutant variants of SARS-CoV2. However, to improve the efficiency of vaccines against the SARS-CoV2 variants that have mutations (changes) in the spike protein, it is important to address all the structural variability present in the Spike protein,” the team added.

The recent study gives structural evidence for the continuous flexibility which can be taken into account while designing future vaccines. “We can hypothesize that spike protein helps the body’s immune system to generate a wide variety of antibodies (broadly neutralizing antibodies bNAbs). Such bNAbs which can recognize altered structural features which are a characteristic of viral mutants could potentially prepare us with a stronger and wider defence mechanism against this deadly virus,” said Dutta.

He said that the data from the study would be shared with vaccine manufacturers.



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Sagar Biswas

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