Researchers at Himachal Pradesh’s IIT Mandi have revealed the part of the structure of a key protein in COVID-19 virus, which helps in understanding its mode of action. Researchers will be able to understand its role in the spread and severity of the disease and development of antiviral therapeutics.
Current COVID-19 treatments, as per the team, simply manage symptoms while the body fights off the infection with its immune defence system. There are, as yet, no confirmed antiviral drugs that can stop the virus from replicating.
Rajanish Giri, Assistant Professor of Biotechnology, IIT Mandi, said one route to neutralizing 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,” he explained.
The virus has 16 non-structural proteins (NSP1-NSP16), of which the NSP1 plays a vital role in the pathogenicity (ability to cause disease) 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.
Giri said that earlier in 2020, they 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 131-180 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.”
The research team has studied the structural conformations of SARS-CoV-2 NSP1 in an organic solvent, membrane mimetic environment and inside liposomes. Using analytical techniques such as circular dichroism spectroscopy, fluorescence spectroscopy and molecular dynamics simulations, the researchers have shown the dynamic changes in the conformation of the IDR of the NSP1 and its interactions with binding partners that are currently unknown.