Giri lab focuses on deciphering the structure-function paradigm and structure-based drug discovery against viral systems such as flaviviruses and coronaviruses. For protein biophysical analysis, we employ different spectroscopic and microscopic techniques such as circular dichroism, fluorescence-based techniques, etc. We integrate computational and pharmacological approaches for further in-vitro investigations.

Our work is sponsored by various prestigious grants from the Department of Science and Technology (DST) - Science and Engineering Research Board (SERB), Department of Biotechnology (DBT), and Indian Council of Medical Research (ICMR), Govt. of India.

INDO-US Symposium on Molecular Virology

Under a program of Scheme for Promotion of Academic and Research Collaboration (SPARC) by the Ministry of Human Resource Development (MHRD), we are organizing a symposium on molecular virology. The well-known scientists and eminent professors are going to discuss the different aspects of virology i.e., pathogenesis, its molecular basis, and the therapeutic strategies against different viruses.

Date of commencement: 15th-17th February 2022

Our recent published articles

Intrinsic disorder in proteins associated with oxidative stress-induced JNK signaling

Highlights of the paper

  1. The presence of intrinsic disorder in proteins of the oxidative stress-induced JNK signaling cascade, and as per our findings, none of the 18 proteins involved in this pathway are ordered.

  2. Highest level of intrinsic disorder was observed in the scaffold proteins, JIP1, JIP2, JIP3; dual specificity phosphatases, MKP5, MKP7; 14-3-3ζ and transcription factor c-Jun.

  3. Molecular recognition features (MoRFs), posttranslational modification (PTM) sites, and short linear motifs (SLiMs) associated with the disordered regions were identified.

Microsecond simulations and CD spectroscopy reveals the intrinsically disordered nature of SARS-CoV-2 spike-C-terminal cytoplasmic tail (residues 1242–1273) in isolation

Highlights of the paper

  1. Available structures of Spike protein of SARS-CoV-2 suggest a missing electron density at its C-terminal region.

  2. Microsecond simulations of C-terminal region (residues 1235–1273 & 1242–1273) shows its intrinsically disordered behavior.

  3. Experimental validations using CD spectroscopy suggests it be an Intrinsically Disordered Protein Region (IDPR).

  4. In presence of molecular crowders like Dextran-70 and PEG 8000, it is also observed to be an IDPR.

The signal peptide of the amyloid precursor protein forms amyloid-like aggregates and enhances Ab42 aggregation

Highlights of the paper

  1. The signal peptide of APP(APP1–17SP) self-assembles into amyloid-like aggregates

  2. APP1–17SP aggregates exhibit amyloid-like morphologies in SEM, TEM, and AFM

  3. APP1–17SP aggregates are cytotoxic to human SH-SY5Y and red blood cells

  4. APP1–17SP seeds augment Ab42aggregation

A novel inhibitor L755507 efficiently blocks c-Myc/MAX heterodimerization and induces apoptosis in cancer cells

Highlights of the paper

  1. The discovery via computer-aided drug discovery of a small molecule, L755507, which functions as a c-Myc inhibitor to efficiently restrict the growth of diverse Myc-expressing cells with low micromolar IC50 values.

  2. L755507 successfully disrupts the c-Myc/MAX heterodimer resulting in decreased expression of c-Myc target genes. Spectroscopic and computational experiments demonstrated that L755507 binds to the c-Myc peptide and thereby stabilizes the helix-loop-helix conformation of the c-Myc transcription factor.

  3. Taken together, this study suggests that L755507 effectively inhibits the c-Myc/MAX heterodimerization and may be used for further optimization to develop a c-Myc targeted antineoplastic drug.

Zika virus capsid anchor forms cytotoxic amyloid-like fibrils

Highlights of the paper

  1. Residues 6th-17th of Zika virus Capsid anchor are predicted amyloid prone region (APR).

  2. Amyloid specific dye-binding assays revealed CA kinetics with shorter initiation phase.

  3. Morphological analysis of aggregates by TEM and AFM revealed characteristic amyloid-like fibrils.

  4. CD spectra of Capsid anchor transitions from disordered/random coil conformation to amyloid fibril specific beta-sheet.

  5. CD spectra of Capsid anchor transitions from disordered/random coil conformation to amyloid fibril specific beta-sheet.

  6. Effect of CA aggregates on mammalian cells and RBCs suggests their cytotoxic and membrane damaging nature.

SARS-CoV-2 NSP1 C-terminal (residues 131-180) is an intrinsically disordered region in isolation

Highlights of paper

  1. Non-structural protein’s residue 131-180 is intrinsically disordered.

  2. SDS and TFE induce alpha-helical conformation in NSP1-CTR.

  3. Neutral lipids showed partial structural changes.

  4. Hydrophobic interactions induce structural changes in NSP1-CTR in the presence of organic solvent.

Small molecule inhibitors possibly targeting the rearrangement of Zika virus envelope protein

Highlights of paper

  1. F1065-0358 inhibits proliferation of ZIKV in Vero cells via blocking the folding back step of E protein during viral entry.

  2. Demonstrates the inhibition ZIKV entry by targeting the Envelope protein rearrangement process.

  3. F1065-0358 interacts with conserved residues of ZIKV E protein suggesting its broad-spectrum potential among flaviviruses.