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.

Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type, and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability allowing a comparative study on the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of darunavir and maybe used for further experimental studies. Our study may also be used as pipeline to search and design new potential inhibitors of HIV-1 proteases.

The increase in antibiotic-resistant bacteria presents a significant risk to worldwide public health, emphasizing the necessity of novel approaches to address infections. Quorum sensing, an essential method of communication among bacteria, controls activities like the formation of biofilms, the production of virulence factors, and the synthesis of secondary metabolites according to the number of individuals in the population. Quorum quenching, which interferes with these processes, emerges as a vital approach to diminish bacterial virulence and prevent biofilm formation. Nanocarriers, characterized by their small size, high surface-area-to-volume ratio, and modifiable surface chemistry, offer a versatile platform for the disruption of bacterial communication by targeting various stages within the quorum sensing pathway. These features allow nanocarriers to infiltrate biofilms, disrupt cell membranes, and inhibit bacterial proliferation, presenting a promising alternative to traditional antibiotics. Integrating nanocarrier-based systems into combination therapies provides a multi-pronged approach to infection control, enhancing both the efficacy and specificity of treatment regimens. Nonetheless, challenges related to the stability, safety, and clinical effectiveness of nanomaterial-based antimicrobial treatments remain. Continued research and development are essential to overcoming these obstacles and fully harnessing the potential of nano-antimicrobial therapies. This review emphasizes the importance of quorum sensing in bacterial behavior and highlights the transformative potential of nanotechnology in advancing antimicrobial treatments, offering innovative solutions to combat antibiotic-resistant pathogens.

Introduction: Antibacterial drug resistance, brought on by the overuse of antibiotics, is one of the biggest threats to human health. It is crucial to consider cutting-edge strategies, such as herbal remedies, to control multidrug-resistant (MDR) bacteria.Methods: This study evaluated the phytochemical, antioxidant and antibacterial properties of the various Tinospora cordifolia extracts. Functionalization of the isolated active compound was done using gold (Au) and silver (Ag) nanoparticles (NPs). Further, to understand the interaction of the isolated class, Cordifolisides, with its target, various in-silico methods were used.Results and Discussion: The plant was reported from the Charaideo district of Assam, whose methanolic stem extract showed the maximum activity towards the nosocomial pathogen Pseudomonas aeruginosa. Consequently, the active compound was isolated and characterized as belonging to the class Cordifoliside using NMR. The AuNPs and AgNPs functionalized isolates showed enhanced antimicrobial activity against P. aeruginosa compared to the unfunctionalized isolate. The most reactive compound, Cordifoliside C was determined using Density Functional Theory (DFT) analysis, whose interactions with the TolB protein were studied using molecular docking methods, which revealed good binding interactions of Cordifoliside C with the TolB protein.Conclusion: This study offers enormous potential for drug design and might be used as a pipeline to address the urgent problem of multidrug-resistance in bacteria.

Introduction: Streptococcus pneumoniae is a Gram-positive bacterium responsible for severe infections such as meningitis and pneumonia. The increasing prevalence of antibiotic resistance necessitates the identification of new therapeutic targets. This study aimed to discover potential drug targets against S. pneumoniae using an in silico subtractive genomics approach.Methods: The S. pneumoniae genome was compared to the human genome to identify non-homologous sequences using CD-HIT and BLASTp. Essential genes were identified using the Database of Essential Genes (DEG), with consideration for human gut microflora. Protein-protein interaction analyses were conducted to identify key hub genes, and gene ontology (GO) studies were performed to explore associated pathways. Due to the lack of crystal structure data, a potential target was modeled in silico and subjected to structure-based virtual screening.Results: Approximately 2,000 of the 2,027 proteins from the S. pneumoniae genome were identified as non-homologous to humans. The DEG identified 48 essential genes, which was reduced to 21 after considering human gut microflora. Key hub genes included gpi, fba, rpoD, and trpS, associated with 20 pathways. Virtual screening of 2,509 FDA-approved compounds identified Bromfenac as a leading candidate, exhibiting a binding energy of −26.335 ± 29.105 kJ/mol.Discussion: Bromfenac, particularly when conjugated with AuAgCu₂O nanoparticles, has demonstrated antibacterial and anti-inflammatory properties against Staphylococcus aureus. This suggests that Bromfenac could be repurposed as a potential therapeutic agent against S. pneumoniae, pending further experimental validation. The approach highlights the potential for drug repurposing by targeting proteins essential in pathogens but absent in the host.