In Silico Pharmacology

UNLABELLED: Alzheimer's disease (AD) is a leading cause of dementia in elderly patients. The pathophysiology of AD includes various pathways, such as the degradation of acetylcholine, amyloid-beta deposition, neurofibrillary tangle formation, and neuroinflammation. Many studies showed that targeting acetylcholinesterase enzyme (AChE) to improve acetylcholine can be an effective option to treat AD. In the current work, we employed a 3D QSAR-based approach to generate a pharmacophore to screen a chemical library of compounds that may inhibit AChE...

UNLABELLED: Oxidative stress is a phenomenon caused by an imbalance between the production and accumulation of reactive oxygen species (ROS) in cells and tissues and the ability of the biological system to detoxify these reactive products. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the most common targets of oxidative stress, and the oxidation of the enzymes causes the inactivation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the formation of disulfide bonds between molecules, leading to aggregates, and eventually to cell death...

UNLABELLED: Neisseria gonorrhoeae , a World Health Organization (WHO) declared superbug and the second-most frequent cause of bacterial sexually transmitted infections worldwide is responsible for gonorrhea. Hypothetical proteins are gene products that are predicted to be encoded by a particular gene based on the DNA sequence, but their specific functions and characteristics have not been experimentally determined or verified. In the context of this research, annotating hypothetical proteins is crucial for identifying their potential as therapeutic targets...

UNLABELLED: Bidens pilosa L. has been traditionally used as an anti-diabetic herbal medicine; however, its mechanism of action remains elusive. In this study, the potential role of B. pilosa compounds on alpha-amylase inhibition and regulation of multiple pathways was investigated via computational and experimental studies. The phytocompounds were retrieved from plant databases and published literature. The druggability profile of these compounds was predicted using MolSoft. The probable targets of these phytocompounds were predicted using BindingDB (similarity index ≥ 0...

UNLABELLED: Uridine 5'-diphospho-glucuronosyltransferases (UGTs) have been considered as a family of enzymes responsible for the glucuronidation process, a crucial phase II detoxification reaction. Among the various UGT isoforms, UGTs A10 and B7 have garnered significant attention due to their broad substrate specificity and involvement in the metabolism of numerous compounds. Recent studies have suggested that certain vitamins may exert inhibitory effects on UGT activity, thereby influencing the metabolism of drugs, environmental toxins, and endogenous substances, ultimately impacting their biological activities...

UNLABELLED: Thyroid hormone (TH) plays a crucial role in regulating the metabolism in every cell and all organs in of the human body. TH also control the rate of calorie burning, body weight, and function of the heartbeat. Therefore, the aim of the present study is to investigate the role of phytocompounds from Brassica oleracea var. italic (Broccoli) against irregularities of TH biosynthesis (hyperthyroidism) through in silico molecular modelling. Initially, the genetic network was built with graph theoretical network analysis to find the right target to control excessive TH production...

Streptococcus uberis is one of the causative agents of bovine mastitis, which has detrimental effects on animal health and the dairy industry. Despite decades of research, the requirement for effective vaccines against the disease remains unmet. The goal of this study was to create a multi-epitope vaccine using five virulence factors of S . uberis through the reverse vaccinology approach, which has been employed due to its high efficiency and applicability. Plasminogen activator A (PauA), glyceraldehyde-3-phosphate dehydrogenase C (GapC), C5a peptidase, S ...

The human respiratory syncytial virus (RSV) creates a pandemic every year in several countries in the world. Lack of target therapeutics and absence of vaccines have prompted scientists to create novel vaccines or small chemical treatments against RSV's numerous targets. The matrix (M) protein and fusion (F) glycoprotein of RSV are well characterized and attractive drug targets. Five bioactive compounds from Alnus japonica (Thunb.) Steud. were taken into consideration as lead compounds. Drug-likeness characters of them showed the drugs are non-toxic and non-mutagenic and mostly lipophobic...

UNLABELLED: Malaria remains a significant public health challenge, with resistance to available drugs necessitating the development of novel therapies targeting invasion-dependent proteins. Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK-1) is essential for host erythrocyte invasion and parasite asexual development. This study screened a library of 490 compounds using computational methods to identify potential PfCDPK-1 inhibitors. Three compounds; 17-hydroxyazadiradione, Picracin, and Epicatechin-gallate derived from known antimalarial botanicals, showed potent inhibitory effects on PfCDPK-1...

UNLABELLED: Pancreatic cancer (PC) presents challenges due to limited treatment options and patients seek complementary therapies alongside conventional treatments to improve well-being. This study uses computational drug discovery approaches to find potential phytochemicals from S. singueana for PC treatment. Among the 38 phytochemicals screened from S. singueana , specific inhibitors against PC were selected. Protein-protein interaction (PPI) network analysis highlighted key targets with high degrees, including PTEN (8) and PTK2 (7) genes, along with their respective proteins 5BZX and 3BZ3, which were employed for molecular docking studies...

The ongoing SARS-CoV-2 pandemic has created an urgent need for effective antiviral drugs that can be rapidly developed and utilized to treat patients infected with the virus. Molnupiravir, a direct-acting oral antiviral, has shown promising results in reducing viral infections with SARS-CoV-2. Nonetheless, there is still a need for the development of more efficacious analogues with enhanced interaction with the specific target, the RNA dependent RNA polymerase (RdRp) and better physico-chemical profile. Our study is based on a rational design strategy, known as "bioisosterism", to design some analogues...

UNLABELLED: Dengue fever presents a major health concern, and the lack of an effective vaccine or definite therapeutic regimen has led the research community to identify safe-by-design potential targets for drug discovery. Since the association of the NS2B co-factor with the protease domain of NS3 is imperative for the catalytic activity of the enzyme complex, inhibitors blocking their interaction could provide an alternative strategy to combat the dengue virus. In this context, the present study is aimed at exploring computer-assisted modeling of significant physicochemical features required for the inhibition of the dengue virus protease complex...

UNLABELLED: The finest sources of therapeutic agents are natural products, and usnic acid is a secondary metabolite derived from lichen that has a wide range of biological actions, including anti-viral, anti-cancer, anti-bacterial, and anti-diabetic (hyperglycemia). Based on the hyperglycemia activity of UA, this work seeks to identify new anti-hyperglycemia medicines by virtual screening of pyrazole derivatives of UA. Seven hit compounds (Compounds 1, 5, 6, 7, 17, 18 and 33), which finally go through docking-based screening to produce the lead molecule, were identified by the physicochemical attributes, drug-likeliness, and ADMET prediction...

UNLABELLED: Diabesity is a major global health concern, and ghrelin O-acyltransferase (GOAT) acts as an important target for the development of new inhibitors of this disease. The present work highlights a detailed QSAR study using QSARINS software, which provides an excellent model equation using descriptors. Here, the best model equation developed has two variables, namely MLFER_E and XlogP, with statistical parameters R2  = 0.8433, LOF = 0.0793, CCCtr = 0...

Occurrence of cancer is driving up on a global scale that exerts greater implications on the physical, psychological and economic stability of the human population. In the present context, numerous research studies are being conducted to explore and discover the drug molecule as an anticancer agent. Diverse scales of flavonoids entail the human diet, and they displayed prospective curative effects against an array of ailments. Among different categories of flavonoids, apigenin a trihydroxy flavone has been proven to have various pharmacological effects...

Neurodegenerative diseases like Alzheimer's have become a growing concern as it is difficult to cure. Tau protein is found to be playing a major role in Alzheimer's disease, and the majority of drugs that are currently on the market are not only prohibitively expensive but also come packaged with side effects that the body cannot tolerate. Repurposing existing compounds is a successful and optimistic strategy that offers reduced risk and increased possibility. We aim to retrieve the existing drugs and analyze them using in-silico techniques...

UNLABELLED: Lung cancer is the cancer of the lung's epithelial cells typically characterized by difficulty breathing, chest pain, blood-stained coughs, headache, and weight loss. If left unmanaged, lung cancer can spread to other body parts. While several treatment methods exist for managing lung cancer, exploring natural plant sources for developing therapeutics offers great potential in complementing other treatment approaches. In this study, we evaluated the bioactive compounds in Vaccinium vitis-idaea for treating KRAS-associated lung cancer types...

UNLABELLED: Vibrio cholerae , the Gram-negative bacterium abruptly colonizes the human intestine causing diarrhea, employing quorum sensing (QS) system as the major survival technique for mediating biofilm formation, virulence, competence, etc. Two distinct QS systems coordinated by the auto-inducer molecules, cholera-specific CqsA/S system and universal LuxS/PQ system, operate in parallel converging into a common phosphorelay pathway involving LuxU and LuxO. The master regulatory proteins of the QS system, AphA and HapR regulate the biofilm formation based on cell density, whose expression is controlled by the global response regulator LuxO...

The main aim of this study is to screen and develop Peptidomimetics to treat atherosclerosis (AS) which is a Cardio Vascular Disease (CVD). Peptidomimetics were obtained from the protein-protein interaction interface of TRADD (Tumor necrosis factor receptor type 1-associated DEATH domain protein) and TRAF2 (TNF receptor-associated factor 2) complex. TRADD-TRAF2 interaction is critical in AS pathogenesis since it assists a series of signal transducers that activate NF-κB. Conceptually, the triggered NF-κB makes an extensive amount of nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS), which boons the progress of AS...

Combination pharmacotherapy is becoming increasingly necessary because most diseases are pathophysiologically controlled at the subcellular level by target proteins in a combinatorial manner. We demonstrate the application of the stimulus-response mechanistic model in characterising the drug and physiological properties of pharmacodynamic drug-drug interactions (PDDI) using previously published in vitro and in vivo drug combination experiments. The in vitro experiment tested the effect of a combination of SCH66336 and 4-HPR on the survival of in squamous cell carcinoma cell lines, while the in vivo experiment tested the effect of a combination of cetuximab and cisplatin on tumour growth inhibition in female xenograft mice...