Chemicals and Drugs Commons^™

Molecular Screening And Dynamics Simulation Reveal Potential Phytocompounds In Swertia Chirayita Targeting The Uspa1 Protein Of Moraxella Catarrhalis For Copd Therapy, Md. Moin Uddin, Md. Shydhur Rahman Chowdhury, Md. Arju Hossain, Asif Ahsan, Md. Tanvir Hossain, Abdul Barik, Md. Arif Hossen, Md. Faisal Amin, Rafsan Abir, Mohammad Shah Alam

School of Integrative Biological & Chemical Sciences Faculty Publications

Chronic obstructive pulmonary disease (COPD) is a global health burden, with Moraxella catarrhalis significantly contributing to acute exacerbations and increased healthcare challenges. This study aimed to identify potential drug candidates in Swertia chirayita, a traditional Himalayan medicinal plant, demonstrating efficacy against the ubiquitous surface protein A1 (UspA1) of M. catarrhalis through an in-silico computational approach. The three-dimensional structures of 46 phytocompounds of S. chirayita were retrieved from the IMPPAT 2.0 database. The structures underwent thorough analysis and screening, emphasizing key factors such as binding energy, molecular docking performance, drug-likeness, and toxicity prediction to assess their therapeutic potential. Considering the …

Lrtm Left-Right Transition Matrices For Molecular Interaction Prediction, Kaitlin Zheng, Guihua Duan, Mengyun Yang, Wei Wu, Yao-Hang Li, Jianxin Wang

Computer Science Faculty Publications

Molecular interactions are central to most biological processes. The discovery and identification of potential associations between molecules can provide insights into biological exploration, diagnostic and therapeutic interventions, and drug development. So far many relevant computational methods have been proposed, but most of them are usually limited to specific domains and rely on complex preprocessing procedures, which restricts the models’ ability to be applied to other tasks. Therefore, it remains a challenge to explore a generalized approach to accurately predicting potential associations. In this study, We propose Left-Right Transition Matrices (LRTM) for molecular interaction prediction. From the perspective on the diffusion …

Cath-Ddg: Towards Robust Mutation Effect Prediction On Protein-Protein Interactions Out Of Cath Homologous Superfamily, Guanglei Yu, Xuehua Bi, Teng Ma, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Protein-protein interactions (PPIs) are fundamental aspects in understanding biological processes. Accurately predicting the effects of mutations on PPIs remains a critical requirement for drug design and disease mechanistic studies. Recently, deep learning models using protein 3D structures have become predominant for predicting mutation effects. However, significant challenges remain in practical applications, in part due to the considerable disparity in generalization capabilities between easy and hard mutations. Specifically, a hard mutation is defined as one with its maximum TM-score < 0.6 when compared to the training set. Additionally, compared to physics-based approaches, deep learning models may overestimate performance due to potential data leakage.

Results: We propose new training/test splits that mitigate data leakage according to the CATH homologous superfamily. Under the constraints of physical …

A Survey On Deep Learning For Drug-Target Binding Prediction: Models, Benchmarks, Evaluation, And Case Studies, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Conventional drug discovery is expensive, time-consuming, and prone to failure. Artificial intelligence has become a potent substitute over the last decade, providing strong answers to challenging biological issues in this field. Among these difficulties, drug-target binding (DTB) is a key component of drug discovery techniques. In this context, drug-target affinity and drug–target interaction are complementary and essential frameworks that work together to improve our comprehension of DTB dynamics. In this work, we thoroughly analyze the most recent deep learning models, popular benchmark datasets, and assessment metrics for DTB prediction. We look at the paradigm shift in the development of drug …

Deepssetracer 2.0: Improved Deep Learning Model Performance For Protein Secondary Structure Segmentation From Cryo-Em Maps, Bryan Hawickhorst, Thu Nguyen, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

DeepSSETracer is a method for segmenting protein secondary structure from medium-resolution (5-10Å) cryogenic electron microscopy (cryo-EM) density maps. We conducted experiments and ablation studies to examine the effects of normalization methods, max-pooling, activation functions, and loss calculation region on DeepSSETracer. By combining multiple technical improvements, the performance of the new version, DeepSSETracer 2.0, was significantly enhanced compared to DeepSSETracer 1.1. On a set of 77 test cases, the weighted average per-voxel F1 score increased from 62.1% to 70.3% for helix detection, and from 47.8% to 62.5% for β-sheet detection. While each of the five modifications in the network enhanced the …

Ribosome Hibernation In Mycobacterium Abscessus And Its Effect On Antibiotic Resistance, Ryan Treen

Electronic Theses & Dissertations (2024 - present)

Non-tuberculosis mycobacteria (NTM) represent a diverse repertoire of species, most of which are ubiquitous in the environment. Some NTM species, such as Mycobacterium abscessus, can cause life-threatening infections in people with underlying medical conditions. The clinical incidence of such infections is on the rise, posing an emerging threat to public health. M. abscessus is characterized by intrinsic and acquired antibiotic resistance, complicating treatment strategies. Most chemotherapeutic approaches for M. abscessus infection target the bacterial ribosome, necessitating a better understanding of the physiological processes which confer this resistance. Multiple mycobacterial species respond to zinc-limiting conditions by inducing remodeling and hibernation …

Synthesis Of Small Molecules As Therapeutic Candidates, Savia Boyer

Electronic Theses & Dissertations (2024 - present)

RNA plays a critical role in many biological functions, such as normal cellular functions or disease-related processes. Regulating biological processes through RNA-based therapeutics can be employed by the reversible photoregulation of oligonucleotides. Azobenzene, a light-responsive compound that changes conformation when exposed to ultraviolet (UV) or visible light, is attached to cytidine phosphoramidite to be incorporated in a series of RNA oligonucleotides. The reversibility of the nucleoside and oligonucleotide is verified through UV melting point experiments. The modified oligonucleotide can change conformation upon light irradiation to stop reverse transcription (RT) in the presence of many different reverse transcriptase enzymes. This technique …

Identifying Notch-Regulated Genes Using A Specific Notch Signaling Inhibitor, Hammed Gafar

EWU Masters Thesis Collection

Bone remodeling is a dynamic process that requires a balance between bone resorption by osteoclasts and bone formation by osteoblasts to maintain skeletal integrity. Disruptions to this equilibrium can lead to pathological conditions such as osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated by several signaling pathways, notably the notch signaling pathway. Gamma-secretase, an enzyme crucial for initiating notch signaling, can be inhibited by DAPT. However, DAPT also targets non-Notch substrates, complicating the identification of genes specifically regulated by Notch. To address this limitation, this study employed IMR-1A, a selective Notch pathway inhibitor that disrupts the assembly of …

Investigating The Production Challenges Of The P100.1 Phage Endolysin, Jonah O. Frago

EWU Masters Thesis Collection

Acne vulgaris is one of the most common skin diseases globally. One key aspect of acne pathogenesis is the disturbance of healthy strain diversity of the skin bacterium Cutibacterium acnes. Many acne treatments are antimicrobial; however, these treatments are generally nonspecific and carry a variety of side effects in addition to contributing to rising antibiotic resistance. Lytic bacteriophages (or phages) are viruses that infect and kill bacteria. Their lytic lifestyle is facilitated by enzymes called endolysins. Phages have been studied as an alternative to traditional antimicrobials in acne treatment and have shown reduced C. acnes load in acne lesions and …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Green Design Of Plant Based Pharmaceutical Drugs: Example Of A Wound Healing Topical Cream With Plectranthus Bojeri (Benth) Hedge Lamiaceae Extract, Helga Rim Farasoa, Marie Louise Razafindravao, Rojo Fanambinantsoa Andriamiarantsoa, Gerard Cecilien Raboanary, Jean Marie Razafindrakoto, Voahangy Ramanandraibe Vestalys

Journal of Bioresource Management

To ensure the perennity of natural resources, the valorisation process of herbal pharmaceuticals must be assessed for sustainability from the very beginning of its design. No specific tools have been developed for this particular field so far. We demonstrate in this study that existing green design tools can be adapted to evaluate plant-based products manufacturing process. As the example of a topical cream using Plectranthus bojeri (Benth) Hedge LAMIACEAE extract was considered, we first confirmed the traditional use of this plant for wound healing. It acts by accelerating the re-epithelialisation phase. Using the Vermeer Cosmolife version 0.24 software tool the …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Glucose-Lowering Agents Developed In The Last Two Decades And Their Perioperative Implications, Basavana Goudra, Geno Merli, Michael Green

Department of Anesthesiology Faculty Papers

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines. Retained gastric contents due to slow gastric emptying is a significant drawback of GLP-1RAs, increasing the risk of aspiration. Recommendations include withholding GLP-1RAs for a predefined period of time, performing gastric ultrasound to evaluate gastric …

Determination Of The Kinetic Parameters Of Cholesterol Oxidation Using Cholesterol Oxidase From Streptomyces Sp., Meka Saima Perdani, Heri Hermansyah, Muhamad Sahlan, Dwini Normayulisa Putri, Teguh Pambudi, Anggi Khairina Hanum Hasibuan

Makara Journal of Technology

Cholesterol oxidase (CO) was successfully produced from Streptomyces sp. via the submerged fermentation method, and 69 U/mL enzyme activity was obtained. This study aimed to determine cholesterol oxidation kinetics and the production of CO as a catalyst. The enzyme was diluted to 0.15, 0.075, and 0.00375 U/mL for the oxidation reaction. The substrate was also prepared in three concentrations: 3.23, 6.46, and 12.93 mM. The optimization of conditions for enzymatic cholesterol oxidation was investigated through measurement of the effect of initial cholesterol and enzyme concentrations. Cholesterol concentration was rapidly measured via high-performance liquid chromatography (HPLC). The kinetics of CO were …

Advancing Continuous Manufacturing: The Role Of Process Analytical Technology In Process Development, Samuel R. Henson

Electronic Theses and Dissertations

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance …

Method Development Of [3 + 2] Cycloadditions Using Tertiary Amine N-Oxides And Efforts Towards The First Total Synthesis Of Chrysosporazine D, Alexander Cocolas

Electronic Theses and Dissertations

Nitrogen-containing heterocycles are ubiquitous in bioactive molecules, pharmaceutical drugs, and natural products. For this reason, finding new and efficient ways to make such compounds remains a high priority for the organic and medicinal community. Our current endeavors build upon previously established work by our group, where we generated 1,2-diamines by coupling commercially available aldehydes with trimethylamine N-oxide (TMAO) in two steps. This route proved to be effective in generating 20+ novel 1,2-diamines and imidazolidines with a demonstrated ability to undergo transformations. Using this chemistry, we have developed a diastereoselective synthesis of 50+ novel 7-azanorbornanes using tertiary amine N-oxides …

Assembly Of Ppsu-Oligomers, Mariam Nesterov

Student Theses and Dissertations

The development of nanostructures for delivering multiple proteins to targeted antibodies has become a promising avenue in biotechnology, driven by advancements in synthetic polymers like poly(propylene sulfone), PPSU. However, the PPSU polymer faces a major limitation - its high insolubility. To address this challenge, this study investigates whether PPSU oligomers can enhance both the solubility and stability of lysozyme, a model protein that is cost-effective and widely accessible. Using dimer, trimer, tetramer, and hexamer configurations, we analyzed the interactions between PPSU oligomer and lysozyme under varying conditions. Our results show that the dimer and trimer are water soluble (no aggregate …

Fda Approves Neffy®- First Nasal Spray For Anaphylaxis, Abigail Carter, Penlope Mazivanhanga, Haylee Whyde, Rileigh Rahrig, Ashley Jacob, Anna Spalvieri, Joshua Honaker, Samantha Mccord, Andrew Roecker

Pharmacy and Wellness Review

Between 1.6 and 5.1% of the United States population have experienced anaphylaxis, a severe allergic reaction.1 Anaphylaxis occurs when someone is exposed to an allergen, most commonly foods, medications, and insect venom. Epinephrine is the first-line agent for anaphylaxis treatment, and it is critical to administer this medication immediately after the onset of anaphylactic symptoms to prevent worsening that could lead to death. Epinephrine, more commonly known as EpiPen® or Auvi-Q®, has historically only been available as an intramuscular (IM) injection. Many people are afraid, anxious, or uneducated on how to properly give someone an IM injection, causing anaphylaxis treatment …

Design And Investigation Of Small Molecule Drugs For Potential Treatment Of Cns Disorders, Flaviviral Infections, And Cancers, Viktoriya Mashinson

Theses & Dissertations

Chapter 1 discusses the development of antagonists against the dopamine 4 receptor (D4R) that is expressed in the motor, associative, and limbic subdivisions of the basal ganglia network and is involved in Parkinson’s disease (PD). Levodopa is the firstline drug for the management of PD symptoms but its long-term use often leads to development of levodopa-induced dyskinesia (LID). D4R antagonists have been shown to decrease the abnormal involuntary movement scores in mouse models of LID. Chapter 1 outlines the development and optimization of selective D4R antagonists for potential treatment of LID. During the investigation of our D4R antagonists we discovered …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …