IIT Mandy reveals key protein structure for Covid-19

A team of researchers at the Indian Institute of Technology Mandy (IIT Mandy), led by Dr. Rajanish Gili, an assistant professor of the Faculty of Basic Sciences, has elucidated some of the important protein structures of the Covid-19 virus. It helps to understand its mechanism of action, its role in the spread and severity of the disease, and the development of antiviral therapeutics.

The team’s recent findings were co-authored by Dr. Giri and his researchers Amit Kumar, Ankur Kumar, Prateek Kumar, and Neha Garg and published in the journal Current Research in Virological Science. Banaras Hindu University.

How are Covid-19 patients treated?

Current Covid-19 treatment only manages symptoms while the body is fighting infection with the immune defense system. No antiviral drug has yet been identified that can block virus replication. One way to neutralize a virus is to attack its protein. Such an approach also applies to the Covif-19 virus, where scientists around the world are involved in research to elucidate the structure and function of these proteins, understand viral diseases, and develop effective drugs against the virus. I have.

In terms of “conformation or” shape “, some proteins contain ordered, essentially chaotic regions. These classical conformations are also found in the SARS-CoV-2 virus protein. The structure of nonstructural protein 1 (NSP1) is composed of 180 amino acids. The first 1-127 region has been ly shown to form an independent structure by Clrak, Green & Petit of the University of Alabama. However, there was no evidence from any group for the 131-180 amino acid region of this NSP1 protein, which plays an important role in suppressing the host’s immune system. With the support of circular dichroism spectroscopy and molecular dynamics simulations, our group at IIT Mandy separated and deciphered the conformations of this region. “Dr. Rajanish Gili, an assistant professor of biotechnology at IIT Mandy, explained.

The virus contains 16 nonstructural proteins (NSP1NSP16), of which NSP1 plays an important role in the pathogenicity of the virus (the ability to cause disease). NSP1 destroys host cell proteins and suppresses their immune function. Its importance can be understood from the fact that it is also called the “host cutoff coefficient”. In particular, NenadBan et al. Found that NSP1 could not stop translation by the ribosome if the C-terminal region of NSP1, or residues 131-180, was removed from NSP1. Therefore, it is important to understand the molecular mechanisms, biophysical interactions, and chemistry of NSP1 interactions with host cells.

“At the beginning of 2020, bioinformatics studies showed that the C-terminal region of NSP1 had a natural denaturation tendency on a scale of 0.4 to 0.5, which is very close to the boundary of intrinsically disordered predictions. Without studies, it was not known whether this 131-180 amino acid region was actually an intrinsically disordered protein region. Generally, these regions are expanded in solution but in host cells. When bound to a particular molecule or partner, it folds into a particular conformation, “said Dr. Rajanish Gili, explaining recent developments in previous studies.

The IIT Mandi team ly studied the structural conformation of SARS-CoV-2NSP1 under a variety of conditions in organic solvents, membrane-mimicking environments, and liposomes. Using analytical techniques such as circular dichroism spectroscopy, fluorescence spectroscopy, and molecular dynamics simulation, researchers have found that the IDR of NSP1 is ambient-dependent due to hydrophobic and electrostatic interactions with proteins. We have shown dynamic changes in conformation. environment.

“Our findings provide valuable insights into the disordered conformation of the NSP1 C-terminal region (residues 131-180) of the SARS-COV2 virus under a variety of environments, broader aspects of NSP1 and its. It helps to understand the interaction with the binding partner, which is currently unknown, “said Dr. Gili.

Understanding the conformational structures and related functions of major viral proteins such as NSP1 will ultimately help develop therapies that can target these proteins and stop the virus by that pathway. Studies such as those done by Dr. Gili and his colleagues can bring this approach closer to reality.

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