Researchers on the Indian Institute of Technology, Mandi (IIT Mandi) in Himachal Pradesh have revealed the a part of structure of a key protein in COVID-19 virus, which helps in understanding its mode of motion, its function within the unfold and severity of the illness and growth of antiviral therapeutics. The findings have been printed in Current Research in Virological Science.
According to the staff, present COVID-19 remedies merely handle signs whereas the physique fights off the an infection with its immune defence system. There are, as but, no confirmed antiviral medicine that may cease the virus from replicating.
“One route to neutralising any virus is to attack its proteins. Such an approach holds true for the COVID-19 virus as well, and scientists across the globe are involved in studies to elucidate the structure and functions of these proteins to understand the viral disease and develop drugs that are effective against the virus,” mentioned Rajanish Giri, Assistant Professor of Biotechnology, IIT Mandi.
This virus has 16 non-structural proteins (NSP1–NSP16), of which the NSP1 performs a significant function within the pathogenicity (capability to trigger illness) of the virus.
“The NSP1 disrupts the proteins of the host cell and suppresses its immune functions. Its importance can be understood by the fact that it is also called the ‘host shutoff factor’. Earlier in 2020, we have shown through bioinformatics studies that NSP1 C-terminal region has intrinsic disorder propensity between 0.4 to 0.5 scales – very close to borderline of intrinsic disorder prediction.
“However, without experimental studies we were not sure that this 13-180 amino acid region is actually an intrinsically disordered protein region. Generally, these regions are unfolded in solution but are folded into particular conformations when binding with specific molecules or partners inside the host cells,” mentioned Giri, explaining the current developments to his earlier analysis.
The IIT Mandi staff has experimentally studied the structural conformations of SARS-CoV-2 NSP1 beneath varied circumstances – in an natural solvent, membrane mimetic setting and inside liposomes.
Using analytical methods akin to round dichroism spectroscopy, fluorescence spectroscopy, and molecular dynamics simulations, the researchers have proven the dynamic adjustments within the conformation of the IDR of the NSP1, in response to its environment, because of hydrophobic and electrostatic interactions between the protein and the setting.
“Our finding provides valuable insight into disorder-order conformation of the NSP1 C-terminal region (residues 131-180) of the SARS-COV2 virus under various environments, which will help in understanding the broader aspect of NSP1 and its interactions with binding partners that are currently unknown,” Giri mentioned. The different members of the staff embody IIT Mandi analysis students Amit Kumar, Ankur Kumar and Prateek Kumar, together with Neha Garg from the Banaras Hindu University.
