Our research focus involves deciphering the dark proteome of different viral systems. Proteins were conventionally thought to be functional with respect to their structure. Contrastingly, disordered proteins and protein regions make up a significant amount of the whole proteome. The flexibility of dark proteome in function of a protein is gaining popularity. Viral proteomes are known to be very small in spite of which viruses are capable of hijacking and interacting with host proteome for their propagation. Specifically, in order to further understand the disorder-function paradigm, we have analyzed the presence of intrinsic disorder in economically important viruses like ZIKV, JEV, CHIKV, rotavirus, and SARS-CoV-2 systems. We also explored the disordered state in proteins of human Ubiquitin-proteasomal system and the Alzheimer’s pathway. The shown video is an example of SARS-CoV-2 Spike glycoprotein cytosolic region.
Structure-based drug discovery
SBDD is a quick, inventive, fool-proof approach to identify therapeutics against biological agents based on structural knowledge about the target. Our lab has optimized in-silico approaches for analysis of protein structures, protein-ligand interactions, and drug design. A few examples of related work from our lab include identification of natural products as potential inhibitors against ZIKV proteins such as envelope, helicase, and protease, the screening of peptidomimetic library against MurA enzyme of Mycobacterium tuberculosis, etc. The shown image is an interaction analysis of Chikungunya protease with compounds.
It is a well-known fact the aggregation is an intrinsic property of proteins, further, unfolded/unstructured have higher tendencies of aggregating. Our lab is fascinated with the prospective role of cellular and viral protein aggregation in pathogenicity associated with infections. We are actively involved in employing computational, biophysical, biochemical, and cellular techniques to investigate mechanisms of protein aggregation and their effects on biological systems. The corresponding image shows the fibril formation by ZIKV capsid anchor protein in all-atom MD simulations.
Small molecule inhibitors possibly targeting the rearrangement of Zika virus envelope protein
Nitin Sharma, Oliver Prosser, Prateek Kumar, Andrew Tuplin, Rajanish Giri. Antiviral Research. 2020 Oct;182:104876. doi: 10.1016/j.antiviral.2020.104876. Epub 2020 Aug 9.
We found that compound F1065-0358 inhibits proliferation of ZIKV in Vero cells via blocking the folding back step of Envelopoe protein during viral entry.