Scientists from IIT Mandi, using spectroscopy and simulation methods, unraveled the molecular structure of a functional spike protein region of the Coronavirus which is responsible for the virus’s infectivity.

The unique and pioneering observations have been recently published in the journal Virology and the research was carried out by Dr Rajanish Giri, Associate Professor at IIT Mandi along with his scholars and Dr Neha Garg, Assistant Professor at Banaras Hindu University.

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The SARS Coronavirus 2, the cause of the ongoing Covid pandemic, is so-called because of the spikes on its surface that give it the appearance of a crown (or corona). The proteins that make up the spikes are responsible for the penetration of these viruses into the host cells of the infected lifeform.

Dr Rajanish Giri said the team has deciphered the shape of the endodomain of spike protein, in isolation, as a reductionist approach. We found that there is no order or structure and this is an intrinsically disordered region.

The endodomain is an important part of spike protein as it contains transporting signals that help in movement of protein inside host cells and thus play a crucial role in infection.

“Due to the absence of specific order or structure, this is the part of Dark Proteome of the virus. It also suggests that endodomain can adopt a fully disordered or partially disordered structure under different conditions. For studying the SARS-CoV-2 spike endodomain, we have used advanced computational algorithms and laboratory techniques. We have also proved, what have only remained speculations so far, the structural flexibilities of the C-terminal region or endodomain,” he said.

The findings can provide direction to the scientific community for the exploration of drugs that can target this region of the spike protein, keeping in mind its structural flexibility. The structural malleability of this region can help identify many new targets inside the host cell, which, in turn, could help in understanding the basic science of Covid-19 and other coronavirus infections.

The researchers have validated the simulation results with experimental studies and have shown that the structure of the intravirion region of the spike protein i.e. endodomain is an intrinsically disordered region in isolation. Also, solvent dependent studies suggest the conformational or shape-changing capabilities of this endodomain.