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Helicobacter pylori (H. pylori) is an infectious agent colonized in gastric epithelium and leads to serious diseases such as ulcers and gastric carcinoma. H. pylori infection requires rapid and effective treatment options however existing therapies gradually diminish in efficacy due to the development of resistance. Type II fatty acid synthesis (FAS-II) pathway is a potent target for drug discovery studies because of its absence in humans and vital necessity for bacteria. In the last step of the synthesis, trans-2-enoyl-ACP is reduced to acyl-ACP with cofactor of NADH by enoyl-ACP reductase, FabI. In this study, recombinant HpFabI was successfully produced using an aLICator ligation-independent cloning and expression vector system for the first time. HpFabI gene was cloned, and then expressed, and the protein was purified in high yield. Recombinant HpFabI with a molecular mass of ~ 30 kDa was confirmed with Western Blot analysis and its concentration was determined in the range of 1.406-3.9495 mg/ml by Bradford Assay. The enzyme-specific activity of HpFabI was determined as 1.5871 nmol min -1  μg -1 by using NADH and crotonoyl-CoA as cofactor and substrate, respectively. HpFabI was produced in high yield to facilitate future inhibition studies including high throughput screening studies for FabI inhibition to contribute novel drug development studies fighting against H. pylori infection., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug repurposing is the strategy of drug utilization for a treatment option other than the intended indications. This strategy has witnessed increased adoption over the past decades, especially within cancer nanomedicine. Cancer nanomedicine has been facilitated through nanoparticle-based (NP-based) delivery systems which can combat nonsmall-cell lung cancer (NSCLC) via recent advances in nanotechnology and apply its benefits to existing drugs. The repurposing of drugs, coupled with NP-based drug delivery systems, presents a promising avenue for achieving effective therapeutic solutions with accelerated outcomes. This review aims to present an overview of NSCLC treatments, with a specific focus on drug repurposing. It seeks to elucidate the latest advances in clinical studies and the utilization of NP-based drug delivery systems tailored for NSCLC treatment. First, the molecular mechanisms of Food and Drug Administration (FDA)-approved drugs for NSCLC, including ROS1 tyrosine kinase inhibitors (TKI) like repotrectinib, approved in November 2023, are detailed. Further, in vitro studies employing a combination strategy of drug repurposing and NP-based drug delivery systems as a treatment approach against NSCLC are listed. It includes the latest study on nanoparticle-based drug delivery systems loaded with repurposed drugs., Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest., (© TÜBİTAK.)

Bacteriodes fragilis is an anaerobic bacterium found in the human intestinal flora. In this study, BfEno was targeted with a structure-based drug design approach because inhibition of this enzyme may prevent both the aerobic and anaerobic pathways due to its role in the glycolytic pathway. First, the gene encoding BfEno was cloned, expressed and the protein produced over 95% purity. The K m and V max values of BfEno were determined as 314.9 µM and 256.2 µmol/min.mg, respectively. Drug-like chemicals were retrieved from the ZINC database for high-throughput virtual screening analyses. As a result of screening study, the ZINC91441604 has been proposed to bind to the active site of the enzyme and remain stable. The same compound exhibited weak binding to the human enolases than the bacterial enolase. Hence, ZINC91441604 may be proposed as a novel candidate for further in vitro and in vivo drug analysis towards the treatment of B. fragilis infections., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, the Nsp12-Nsp8 complex of SARS-CoV-2 was targeted with structure-based and computer-aided drug design approach because of its vital role in viral replication. Sequence analysis of RNA-dependent RNA polymerase (Nsp12) sequences from 30,366 different isolates were analysed for possible mutations. FDA-approved and investigational drugs were screened for interaction with both mutant and wild-type Nsp12-Nsp8 interfaces. Sequence analysis revealed that 70.42% of Nsp12 sequences showed conserved P323L mutation, located in the Nsp8 binding cleft. Compounds were screened for interface interaction, any with XP GScores lower than -7.0 kcal/mol were considered as possible interface inhibitors. RX-3117 (fluorocyclopentenyl cytosine) and Nebivolol had the highest binding affinities in both mutant and wild-type enzymes, therefore they were selected and resultant protein-ligand complexes were simulated for analysis of stability over 100 ns. Although the selected ligands had partial mobility in the binding cavity, they were not removed from the binding pocket after 100 ns. The ligand RX-3117 remained in the same position in the binding pocket of the mutant and wild-type enzyme after 100 ns MD simulation. However, the ligand Nebivolol folded and embedded in the binding pocket of mutant Nsp12 protein. Overall, FDA-approved and investigational drugs are able to bind to the Nsp12-Nsp8 interaction interface and prevent the formation of the Nsp12-Nsp8 complex. Interruption of viral replication by drugs proposed in this study should be further tested to pave the way for in vivo studies towards the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 has caused COVID-19 outbreak with nearly 2 M infected people and over 100K death worldwide, until middle of April 2020. There is no confirmed drug for the treatment of COVID-19 yet. As the disease spread fast and threaten human life, repositioning of FDA approved drugs may provide fast options for treatment. In this aspect, structure-based drug design could be applied as a powerful approach in distinguishing the viral drug target regions from the host. Evaluation of variations in SARS-CoV-2 genome may ease finding specific drug targets in the viral genome. In this study, 3458 SARS-CoV-2 genome sequences isolated from all around the world were analyzed. Incidence of C17747T and A17858G mutations were observed to be much higher than others and they were on Nsp13, a vital enzyme of SARS-CoV-2. Effect of these mutations was evaluated on protein-drug interactions using in silico methods. The most potent drugs were found to interact with the key and neighbor residues of the active site responsible from ATP hydrolysis. As result, cangrelor, fludarabine, folic acid and polydatin were determined to be the most potent drugs which have potency to inhibit both the wild type and mutant SARS-CoV-2 helicase. Clinical data supporting these findings would be important towards overcoming COVID-19., (Copyright © 2020 Elsevier B.V. All rights reserved.)