Current applications of nanoparticles in infectious diseases.

Nano-therapeutics: A revolution in infection control in post antibiotic era.

The binding of two bio-active flavonoids, quercetin and rutin, with bovine hemoglobin (BHb) was investigated by multi-spectroscopic and computational (molecular docking and molecular dynamics simulation) studies. The two flavonoids were found to quench the intrinsic fluorescence of BHb through a static quenching mechanism. The binding constants at 288 K were observed to be (14.023 ± 0.73) × 104 M-1 and (7.848 ± 0.20) × 104 M-1, respectively for quercetin and rutin binding with BHb. Both rutin and quercetin were observed to increase the polarity around the Trp residues of BHb as indicated by synchronous and 3D spectral studies. No significant alterations in the secondary structural components of the protein were caused during the binding of the flavonoids as studied by CD and FTIR studies. The negative molar Gibbs free energies indicated the spontaneity of the interaction processes while the binding processes were characterized by a negative enthalpy change (ΔH) and a positive entropy change (ΔS). The possibility of energy transfer from the donor (BHb) to the acceptor molecules (flavonoids) was indicated by the FRET studies. According to the fluorescence studies, the flavonoids interact near to the β2-Trp37 residue of BHb. Excellent correlations with the experimental studies were observed from the molecular docking and molecular dynamics (MD) simulation studies. Further investigations established that these flavonoids are efficient in the inhibition of glucose mediated glycation of BHb.

Molecular recognition of bio-active flavonoids quercetin and rutin by bovine hemoglobin: an overview of the binding mechanism, thermodynamics and structural aspects through multi-spectroscopic and molecular dynamics simulation studies.

The recent advancement of low-dimensional nanostructured materials for drug delivery and drug sensing application: A brief review

In recent years research based on kaempferol (KMP) has shown its potential therapeutic applications in medicinal chemistry and clinical biology. Therefore, to understand its molecular recognition mechanism, we studied its interactions with the carrier proteins, namely, human serum albumin (HSA), bovine hemoglobin (BHb) and hen egg white lysozyme (HEWL). The ligand, KMP was able to quench the intrinsic fluorescence of these three proteins efficiently through static quenching mode. The binding constant (Kb) for the interactions of KMP with these three proteins were found in the following order: HSA-KMP > BHb-KMP > HEWL-KMP. Different non-covalent forces such as hydrogen bonding and hydrophobic forces played a major role in the binding of KMP with HSA and HEWL, whereas hydrogen bonding and van der Waals forces contribute to the complexation of BHb with KMP. KMP was able to alter the micro-environment near the Trp fluorophore of the proteins. KMP altered the secondary structural component of all three proteins. The putative binding sites and the residues surrounding the KMP molecule within the respective protein matrix were determined through molecular docking and molecular dynamics (MD) simulation studies. The conformational flexibility of the ligand KMP and the three individual proteins were also evident from the MD simulation studies.

Exploring the interaction of bioactive kaempferol with serum albumin, lysozyme and hemoglobin: A biophysical investigation using multi-spectroscopic, docking and molecular dynamics simulation studies.

The potential biomedical application of carbon nanotubes (CNTs) pertinent to drug delivery is highly manifested considering the remarkable electronic and structural properties exhibited by CNT. To simulate the interaction of nanomaterials with biomolecular systems, we have performed density functional calculations on the interaction of pyrazinamide (PZA) drug with functionalized single-wall CNT (fSWCNT) as a function of nanotube chirality and length using two different approaches of covalent functionalization, followed by docking simulation of fSWCNT with pncA protein. The functionalization of pristine SWCNT facilitates in enhancing the reactivity of the nanotubes and formation of such type of nanotube-drug conjugate is thermodynamically feasible. Docking studies predict the plausible binding mechanism and suggests that PZA loaded fSWCNT facilitates in the target specific binding of PZA within the protein following a lock and key mechanism. Interestingly, no major structural deformation in the protein was observed after binding with CNT and the interaction between ligand and receptor is mainly hydrophobic in nature. We anticipate that these findings may provide new routes towards the drug delivery mechanism by CNTs with long term practical implications in tuberculosis chemotherapy.

Density functional and molecular docking studies towards investigating the role of single-wall carbon nanotubes as nanocarrier for loading and delivery of pyrazinamide antitubercular drug onto pncA protein.

Drug repurposing is a more inexpensive and shorter approach than the traditional drug discovery and development process. The concept of identifying a potent molecule from a library of pre-existing molecules or an already approved drug has become a go-to tactic to accelerate the identification of drugs that can prevent COVID-19. This seemingly uncontrollable disease is caused by SARS-CoV-2. It is a novel virus of the Betacoronavirus genus, exhibiting similarities to the previously reported SAR-CoV genome structure and viral pathogenesis. The emergence of SARS-CoV-2 and the rapid outbreak of COVID-19 have resulted in a global pandemic. Researchers are hard-pressed to develop new drugs for total containment of the disease, thus making the cost-effective drug repurposing a much more feasible approach. Therefore, the current review attempts to collate both the experimental and computational drug repurposing strategies that have been utilized against significant drug targets of SARS-CoV-2. Along with the strategies, the available druggable targets shall also be discussed. However, the occurrence of frequent recombination of the viral genome and time-bound primary analysis, resulting in insignificant data, are two major challenges that drug repurposing still faces.

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

InhA is an attractive target to combat tuberculosis (TB), which is targeted by many pro-drugs (isoniazid, etc.) and drugs such as triclosan. However, triclosan is less useful as an antitubercular drug due to its low bioavailability and therefore, in order to overcome this difficulty, many derivatives of triclosan were prepared. Here, we have combined various computational techniques to virtually screen out four potential triclosan derivatives. Molecular docking methods have been employed to screen out 32 out of 62 triclosan derivatives considering the mode of binding and the top re-rank scores. A comparative study on the chemical properties of triclosan and some of its derivatives has been performed using density functional theory (DFT) calculations. DFT based global reactivity descriptors (GRD), such as hardness, chemical potential, chemical softness, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries were used to investigate the usefulness of these descriptors for understanding the reactive nature and sites of the molecules. QSAR equations were built using these descriptors considering these 32 compounds. Four common compounds showing the best correlation and the best docking scores were considered for the ADMET property calculations and their dynamical movements have been studied using molecular dynamics simulations. Our results showed that these four compounds are chemically more active than triclosan and have the potential to inhibit the Mycobacterium tuberculosis enoyl acyl carrier protein reductase. This work shows that combination of different computational techniques may help to screen out potential drug candidates from a list of possible ones.

Anti-tubercular drug development: computational strategies to identify potential compounds

Design of Plasmodium falciparum PI(4)KIIIβ Inhibitor using Molecular Dynamics and Molecular Docking Methods

Tuberculosis caused by Mycobacterium tuberculosis is an infectious bacterial disease which is a leading cause of mortality affecting more than 9 million people worldwide. The current standard regimens that are available for the treatment of TB are severely hampered due to the occurrence of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of Mycobacterium tuberculosis. In the past few years, a huge and constantly expanding effort has been developed to understand the chemical-biological interaction of many new anti-tubercular drugs and their targets in mathematical terms. Here, we have elected to review only those studies concerning 2D and 3D QSAR models that contain different DFT based descriptors as their parameters.

Sanchaita Rajkhowa

Papers

Density functional and molecular docking studies towards investigating the role of single-wall carbon nanotubes as nanocarrier for loading and delivery of pyrazinamide antitubercular drug onto pncA protein.

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Anti-tubercular drug development: computational strategies to identify potential compounds

Design of Plasmodium falciparum PI(4)KIIIβ Inhibitor using Molecular Dynamics and Molecular Docking Methods

DFT Based QSAR/QSPR Models in the Development of Novel Anti-tuberculosis Drugs Targeting Mycobacterium tuberculosis