Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.

Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.

Eperisone hydrochloride (EH) is widely used as a muscle relaxant for patients with muscular contracture, low back pain, or spasticity. Human serum albumin (HSA) is a highly soluble negatively charged, endogenous and abundant plasma protein ascribed with the ligand binding and transport properties. The current study was undertaken to explore the interaction between EH and the serum transport protein, HSA. Study of the interaction between HSA and EH was carried by UV-vis, fluorescence quenching, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, Förster's resonance energy transfer, isothermal titration calorimetry and differential scanning calorimetry. Tryptophan fluorescence intensity of HSA was strongly quenched by EH. The binding constants (K) were obtained by fluorescence quenching, and results show that the HSA-EH interaction revealed a static mode of quenching with binding constant K ≈ 10 reflecting high affinity of EH for HSA. The negative ΔG° value for binding indicated that HSA-EH interaction was a spontaneous process. Thermodynamic analysis shows HSA-EH complex formation occurs primarily due to hydrophobic interactions, and hydrogen bonds were facilitated at the binding of EH. EH binding induces α-helix of HSA as obtained by far-UV CD and FTIR spectroscopy. In addition, the distance between EH (acceptor) and Trp residue of HSA (donor) was calculated 2.18 nm using Förster's resonance energy transfer theory. Furthermore, molecular docking results revealed EH binds with HSA, and binding site was positioned in Sudlow Site I of HSA (subdomain IIA). This work provides a useful experimental strategy for studying the interaction of myorelaxant with HSA, helping to understand the activity and mechanism of drug binding.

Tolperisone hydrochloride (TH) has muscle relaxant activity and has been widely used for several years in clinical practice to treat pathologically high skeletal muscle tone (spasticity) and related pains. The current study was designed to explore the binding efficacy of TH with human serum albumin (HSA) using multispectrscopic, calorimetric approach, FRET, esterase-like activity, and a molecular docking method. A reduction in fluorescence emission at 340 nm of HSA was attributed to fluorescence quenching by TH via a static quenching type. Binding constants ( K) were evaluated at different temperatures, and obtained K values were ∼10 M, which demonstrated moderately strong affinity of TH for HSA. A calculated negative Δ G° value indicated spontaneous binding of TH to HSA. Far-UV CD spectroscopy revealed that the α-helix content was increased after TH binding. The binding distance between donor and acceptor was calculated to be 2.11 nm based on Förster's resonance energy transfer theory. ITC results revealed TH interacted with HSA via hydrophobic interactions and hydrogen bonding. The thermal stability of HSA was studied using DSC, and results showed that in the presence of TH the structure of HSA was significantly more thermostable. The esterase-like activity of HSA showed fixed V and increased K suggesting that TH binds with HSA in a competitive manner. Furthermore, molecular docking results revealed TH binds in the cavity of HSA, that is, subdomain IIA (Sudlow site I), and that it hydrogen bonds with K199 and H242 of HSA. Binding studies of drugs with HSA are potentially useful for elucidating chemico-biological interactions that can be utilized in the drug design, pharmaceutical, pharmacology, and biochemistry fields. This extensive study provides additional insight of ligand binding and structural changes induced in HSA relevant to the biological activity of HSA in vivo.

A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds