Insight into the Interaction and Inhibition of NS3 ATPase of Dengue Virus with 3′-Azido-3′-deoxythymidine: Computational and Biophysical Approaches Ayesha Tazeen, Tanzeel Khan, Abdus Samad, Anwar Ahmed, Zulfiqar Ahmad, Asimul Islam, Shama Parveen ACS Omega, 2026 ). Isothermal titration calorimetry (ITC) measurements revealed strong and spontaneous binding between NS3 and AZT-TP with feasible thermodynamic parameters. The ATPase inhibition assay showed a decrease in NS3 ATPase activities in a dose-dependent manner, indicating the inhibitory potential of AZT-TP. Molecular docking showed significant binding (-8.0 kcal/mol) with the conserved residues involved in NS3 helicase/ATPase activities. Molecular dynamics (MD) simulation studies showed no major conformational changes in the NS3 and AZT-TP complex, and it was well-anchored at its binding position with nearly a linear trajectory up to 200 ns. Total Gibbs free energy and contribution of different interactions calculated using MMPB-(GB)-SA complemented the biophysical and docking results. The study suggests that there might be a direct binding between AZT-TP and residues involved in the ATPase activities and thus provides promising data to explore the future prospects of AZT-TP as an NS3 inhibitor for antiviral development.
Stability and Conformational Dynamics of Interferons: Structural Insights into the Urea- and Guanidinium Chloride-Induced Unfolding Ayesha Aiman, Faizan Ahmad, Priyanka Kataria, Amresh Prakash, Faiza Iram, Tanzeel Khan, Seemi Farhat Basir, Luqman Ahmad Khan, Mohammad Shahid, Md. Imtaiyaz Hassan, Asimul Islam ACS Omega, 2026 Interferon-β is a β-helical cytokine that plays a critical role in modulating neuroinflammatory pathways. We measured the stability of IFN-β, associated with equilibrium, in terms of change in Gibbs free energy (ΔGD0) between the folded (N) and denatured (D) states in the native buffer (i.e., during the absence of strong chemical denaturants, Guanidinium chloride (GdmCl) and urea are known to destroy noncovalent interactions responsible for maintaining the folded state). We have deliberated on the denaturation of IFN-β at 25 °C and pH 7.5 using two different spectroscopic probes, namely, fluorescence emission maxima (λmax, nm) and circular dichroism (ellipticity, θ in millidegrees) at 222 nm. From these in vitro studies, we reached the following conclusions: (i) Both denaturants induce a single step (“N” to “D”) transition. (ii) Denaturation of IFN-β protein is irreversible. (iii) Protein stability in terms of ΔGD0 is very low (ΔGD0 = ± 3.12 kcal·mol–1), which is likely due to the presence of hydrophobic patches (nonpolar side chains) on the surface of the native protein as shown by ANS (8-anilinonaphthalene-1-sulfonic acid) steady-state measurements. Atomistic simulations were conducted to obtain detailed molecular insights into the structural changes occurring with increased denaturant concentration (6 M GdmCl and 8 M urea) for a period of 500 ns in water at different temperatures (300–500 K). The analysis of results obtained from simulations corroborates those obtained from in vitro measurements. This investigation is the first comprehensive analysis of the unfolding trajectories of IFN-β under different denaturants.
Urea induced characterization & structural dynamics of the Nucleocapsid Protein using biophysical and in silico approaches Abdus Samad, Md Ali Imam, Danish Alam, Anwar Ahmed, Asimul Islam, Shama Parveen Journal of Molecular Structure, 2026 • Nucleocapsid protein (N) of SARS CoV-2 is loses its tertiary and secondary structure under urea induced denaturation • Differential scanning calorimetry measured the global changes during the denaturation process, revealing slight increase in Tm with increasing concentration of urea • The increase in Tm along with decrease in Δ Cp value inferred the formation of intermediate like state The Nucleocapsid (N) protein of SARS CoV-2 is multifunctional protein whose role is not limited to replication but also in attenuation of the host immune response. Since N protein is abundantly present and post infection, it becomes essential to understand the structural dynamics of the N protein in absence of high-resolution crystal structure. In this study, the structural and conformational dynamics of the recombinant N protein was studied through circular dichroism (CD), fluorescence spectroscopy and differential scanning calorimetry (DSC) under urea induced denaturing conditions. The biophysical studies revealed that N protein loses its tertiary structure cooperatively starting from 2.00 M of urea induced denaturation with a redshift in λ max . The CD spectroscopy revealed that there is loss in random coil content hence secondary structure content and shifting of θ max towards higher wavelength. The DSC experiments revealed increase in T m along with decrease in Δ C p value inferring formation of intermediate like state. All the in vitro studies were further complimented using 300 ns MD simulation using Gromacs 2022.2. These data provide information of structural characteristics and dynamics of the N protein in absence of high-resolution crystal structure and redefine the current understanding of structure of the N protein. Furthermore, pave way for the development of antiviral drugs targeting the N protein to complement the existing vaccine in case of emergence of neutralization escape mutant.
Antibiotic adjuvants: synergistic tool to combat multi-drug resistant pathogens Vikram Kumar, Nusrath Yasmeen, Aishwarya Pandey, Anis Ahmad Chaudhary, Abdullah S. Alawam, Hassan Ahmad Rudayni, Asimul Islam, Sudarshan S. Lakhawat, Pushpender K. Sharma, Mohammad Shahid Frontiers in Cellular and Infection Microbiology, 2023
FNDC5/Irisin: Physiology and Pathophysiology Rashid Waseem, Anas Shamsi, Taj Mohammad, Md. Imtaiyaz Hassan, Syed Naqui Kazim, Anis Ahmad Chaudhary, Hassan Ahmed Rudayni, Mohammed Al-Zharani, Faizan Ahmad, Asimul Islam Molecules, 2022
Potential drug targets of SARS-CoV-2: From genomics to therapeutics Anas Shamsi, Taj Mohammad, Saleha Anwar, Samreen Amani, Mohd Shahnawaz Khan, Fohad Mabood Husain, Md. Tabish Rehman, Asimul Islam, Md Imtaiyaz Hassan International Journal of Biological Macromolecules, 2021
