Virtual screening

Antibiotic resistance in Gram-negative bacteria remains one of the most pressing challenges to global public health. Blocking the transportation of lipopolysaccharides (LPS), a crucial component of the outer membrane of Gram-negative bacteria, is considered a promising strategy for drug discovery. In the transportation process of LPS, two components of the LPS transport (Lpt) complex, LptA and LptC, are responsible for shuttling LPS across the periplasm to the outer membrane, highlighting their potential as targets for antibacterial drug development...

Breast cancer is a major global health issue, causing high incidence and mortality rates as well as psychological stress for patients. Chemotherapy resistance is a common challenge, and the Aldo-keto reductase family one-member C3 enzyme is associated with resistance to anthracyclines like doxorubicin. Recent studies have identified celecoxib as a potential treatment for breast cancer. Virtual screening was conducted using a quantitative structure-activity relationship model to develop similar drugs; this involved backpropagation of artificial neural networks and structure-based virtual screening...

Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA methods are used to establish models of 65 imidazo[4,5- b ]pyridine derivatives to explore the quantitative structure-activity relationship between their anticancer activities and molecular conformations. The results show that the cross-validation coefficients q 2 of HQSAR, CoMFA, CoMSIA and TopomerCoMFA are 0.892, 0...

Pyxinol, an active metabolite of ginsenosides in human hepatocytes, exhibits various pharmacological activities. Here, a series of C-3 modified pyxinol derivatives was designed and virtually screened by molecular docking with the key inflammation-related proteins of the nuclear factor kappa B (NF-κB) pathway. Some of the novel derivatives were synthesized to assess their effects in inhibiting the production of nitric oxide (NO) and mitochondrial reactive oxygen species (MtROS) in lipopolysaccharide-triggered RAW264...

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The transketolase 1 gene (TKTL1) is an essential factor that contributes to brain development. Some studies have shown the influence of TKTL1 in cancers, but it has been rarely reported in kidney cancer. Furthermore, the role of TKTL1 in the prognosis and tumor infiltration of immune cells in various cancers, particularly kidney cancer, remains unknown. In this study, TKTL1 expression and its clinical characteristics were investigated using a variety of databases. TIMER was used to investigate the relationship between TKTL1 and immune infiltrates in various types of cancer...

This study aimed to investigate the impact of a common non-synonymous gene variant (C>G, rs738409) in patatin-like phospholipase domain-containing 3 ( PNPLA3 ), leading to the substitution of isoleucine with methionine at position 148 ( PNPLA3 -I148M), on susceptibility to nonalcoholic fatty liver disease (NAFLD) and explore potential therapeutic nutritional strategies targeting PNPLA3 . It contributed to understanding sustainable dietary practices for managing NAFLD, recently referred to as metabolic-dysfunction-associated fatty liver...

Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance...

Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation...

There is a high demand for agonist biomolecules such as cytokine surrogates in both biological and medicinal research fields. These are typically sourced through natural ligand engineering or affinity-based screening, followed by individual functional validation. However, efficient screening methods for identifying rare hits within immense libraries are very limited. In this research article, we introduce a phenotypic screening method utilizing biological receptor activation-dependent cell survival (BRADS)...

Action observation and motor imagery (AOMI) are commonly delivered through a laptop screen. Immersive virtual reality (VR) may enhance the observer's embodiment, a factor that may boost AOMI effects. The study aimed to investigate the effects on manual dexterity of AOMI delivered through immersive VR compared to AOMI administered through a laptop. To evaluate whether VR can enhance the effects of AOMI, forty-five young volunteers were enrolled and randomly assigned to the VR-AOMI group, who underwent AOMI through immersive VR, the AOMI group, who underwent AOMI through a laptop screen, or the control group, who observed landscape video clips...

BACKGROUND: The COVID-19 pandemic has resulted in widespread disruptions to primary healthcare delivery and shifts to virtual care. Reduced in-person paediatric primary care visit rates have been reported. However, the extent to which access to primary preventative care has been impacted remains unclear. The objective of this scoping review is to characterise the utilisation of preventative primary care and its association with child development for children ages 0-5 years old during the COVID-19 era...

BACKGROUND: 3D visualization technology applies computers and other devices to create a realistic virtual world for individuals with various sensory experiences such as 3D vision, touch, and smell to gain a more effective understanding of the relationships between real spatial structures and organizations. The purpose of this study was to comprehensively evaluate the effectiveness of 3D visualization technology in human anatomy teaching/training and explore the potential factors that affect the training effects to better guide the teaching of classroom/laboratory anatomy...

Pneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pneumoniae, the main cause for bacterial pneumonia. Liberation of PLY during infection leads to compromised immune system and cytolytic cell death. Here, we report discovery, development, and validation of targeted small molecule inhibitors of PLY (pore-blockers, PB). PB-1 is a virtual screening hit inhibiting PLY-mediated hemolysis. Structural optimization provides PB-2 with improved efficacy. Cryo-electron tomography reveals that PB-2 blocks PLY-binding to cholesterol-containing membranes and subsequent pore formation...

Diabetes is a chronic disease that is characterized by high blood sugar levels and can have several harmful outcomes. Hyperglycemia, which is defined by persistently elevated blood sugar, is one of the primary concerns. People can improve their overall well-being and get optimal health outcomes by prioritizing diabetes control. Although the use of experimental approaches in diabetes treatment is cost-effective, it necessitates the development of many strategies for evaluating the efficacy of therapies. Researchers can quickly create new strategies for managing diabetes and get vital insights by enabling virtual screening with computational tools and procedures...

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 μM, which is less potent than benzbromarone (2.01 ± 0.36 μM) but more potent than lesinurad (10...

The discovery of novel therapeutic agents with potent anticancer activity remains a critical challenge in drug development. Natural products, particularly bioactive phytoconstituents derived from plants, have emerged as promising sources for anticancer drug discovery. In this study, we used virtual screening techniques to explore the potential of bioactive phytoconstituents as inhibitors of fibroblast growth factor receptor 1 (FGFR1), a key signaling protein implicated in cancer progression. We used virtual screening techniques to analyze phytoconstituents extracted from the IMPPAT 2...

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives...

Nowadays, the explosion of knowledge in the field of epigenetics has revealed new pathways toward the treatment of multifactorial diseases, rendering the key players of the epigenetic machinery the focus of today's pharmaceutical landscape. Among epigenetic enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest in DNMTs has led to advanced experimental and computational strategies in the search for novel DNMT inhibitors. Considering the importance of epigenetic targets as a novel and promising pharmaceutical trend, the present study attempted to discover novel inhibitors of natural origin against DNMTs using a combination of structure and ligand-based computational approaches...