Abstract Background Nuclear Factor kappa B (NF-κB) is a transcription factor involved in the regulation of cell signaling responses and key regulator cellular processes immune response, differentiation, proliferation, apoptosis. The constitutive activation NF-κB contributes to multiple outcomes pathophysiological conditions such as rheumatoid arthritis, asthma, inflammatory bowel disease, AIDS cancer. Thus there lies huge therapeutic potential beneath inhibition signalling pathway for...

Abstract Background HSPs (Heat shock proteins) are highly conserved ubiquitous proteins among species which involved in maintaining appropriate folding and conformation of other thus referred to as molecular chaperones. Hsp90 (Heat-shock protein 90 kDa) is one a group chaperones responsible for managing quality control cell environment. However it also the maturation stabilization wide range oncogenic client crucial oncogenesis malignant progression. requires series co-chaperones assemble...

p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair prevent malignant transformation. MDM2 regulates activity of p53 inhibits its binding DNA. In present study, we elucidated inhibition potential polyphenols (Apigenin, Fisetin, Galangin Luteolin) by MD simulation MM/PBSA free energy calculations. All bind hydrophobic groove was found be stable throughout simulation. Luteolin showed highest negative value -173.80 kJ/mol followed Fisetin with...

Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for variety of health promoting and therapeutic potentials.We investigated the molecular mechanism anticancer anti-metastasis activities CAPE.cDNA array performed on control CAPE-treated breast cancer cells revealed activation DNA damage signaling involving upregulation GADD45α p53 tumor suppressor proteins.Molecular docking analysis that CAPE capable disrupting mortalin-p53 complexes.We provide...

Abstract Adverse drug reactions (ADRs) have become one of the primary reasons for failure drugs and a leading cause deaths. Owing to severe effects ADRs, there is an urgent need generation effective models which can accurately predict ADRs during early stages development based on integration various features drugs. In current study, we focused neurological used properties that include biological (targets, transporters enzymes), chemical (substructure fingerprints), phenotypic (side (SE)...

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M.tb), causes highest number of deaths globally for any bacterial necessitating novel diagnosis and treatment strategies. High-throughput sequencing methods generate a large amount data which could be exploited in determining multi-drug resistant (MDR-TB) associated mutations. The present work is computational framework that uses artificial intelligence (AI) based machine learning (ML) approaches predicting...

Coronavirus pandemic has caused a vast number of deaths worldwide. Thus creating an urgent need to develop effective counteragents against novel coronavirus disease (COVID-19). Many antiviral drugs have been repurposed for treatment but implicated minimal recovery, which further advanced the clearer insights and innovation derive therapeutics. Strategically, Noscapine, approved antitussive drug with positive effects on lung linings may show favorable outcomes synergistically in trials....

Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores encephalitis. Previous antiviral studies on herpes viruses have focussed developing nucleoside analogues that can inhibit viral polymerase terminate the replicating DNA. However, these drugs bear an intrinsic non-specificity as they also cellular apart from one. The present study is attempt to elucidate action mechanism of naturally occurring withaferin A inhibiting DNA polymerase, thus providing evidence...

Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells takes place leading to loss memory and decreased cognitive ability. AD cause worldwide progressive nature with symptoms worsening over time. Machine learning-based computational predictive models based on 2D 3D descriptors have been effective identifying potential active compounds. However, use data from molecular dynamics (MD) trajectories for training machine learning still needs be explored. In...

Abstract Tuberculosis is one the oldest known affliction of mankind caused by pathogen Mycobacterium tuberculosis . Till date, there no absolute single treatment available to deal with pathogen, which has acquired a great potential develop drug resistance rapidly. BCG only anti-tuberculosis vaccine till date displays limited global efficacy due genetic variation and concurrent infections. Extracellular vesicles or exosomes vesicle (EVs) lie at frontier cellular talk between host, therefore...

Abstract Background The UPP (ubiquitin proteasome pathway) is the major proteolytic system in cytosol and nucleus of all eukaryotic cells which regulates cellular events, including mitotis, differentiation, signal transduction, apoptosis, inflammation. controls activation transcriptional factor NF-κB (nuclear κB), a regulatory protein playing central role variety processes immune inflammatory responses, proliferation. Since primary interaction proteasomes occurs with endogenous proteins,...

Abstract Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia. So far only five drugs have been approved by US FDA that temporarily slow worsening symptoms for about six to twelve months. The limited number therapeutic options AD drives exploration new drugs. Enhancement central cholinergic function inhibition acetylcholinesterase prominent clinically effective approach treatment AD. Recently withanolide A, secondary metabolite from ayurvedic plant...

Cancer is largely marked by genetic instability. Specific inhibition of individual proteins or signalling pathways that regulate stability during cell division thus hold a great potential for cancer therapy. The Aurora A kinase Ser/Thr plays critical role mitosis and cytokinesis found upregulated in several types. It functionally regulated its interactions with TPX2, candidate oncogene. inhibitors have been proposed as anticancer drugs work blocking ATP binding site. This site common to...

Leishmaniasis is caused by several species of leishmania protozoan and one the major vector-born diseases after malaria sleeping sickness. Toxicity available drugs drug resistance development protozoa in recent years has made cure difficult challenging. This urges need to discover new antileishmanial-drug targets development.Tertiary structure leishmanial protein kinase C was predicted found stable with a RMSD 5.8Å during MD simulations. Natural compound withaferin A inhibited at its active...

Propolis, a resinous substance collected by honeybees mixing their saliva with plant sources, including tree bark and leaves then mixed secreted beeswax, possesses variety of bioactivities. Whereas caffeic acid phenethyl ester (CAPE) has been recognized as major bioactive ingredient in New Zealand propolis, Brazilian green on the other hand, artepillin C (ARC). In this study, we report that, similar to CAPE, ARC docks into abrogates mortalin-p53 complexes, causing activation p53 growth...

Embelin, a natural quinone found in the fruits of Embelia ribes, is commonly used Ayurvedic home medicine for variety therapeutic potentials including anti-inflammation, anti-fever, anti-bacteria and anti-cancer. Molecular mechanisms these activities cellular targets have not been clarified to-date. We demonstrate that embelin inhibits mortalin-p53 interactions, activates p53 protein tumor cells. provide bioinformatics, molecular docking experimental evidence to binding affinity with...

Abstract Pyrazinamide is an essential first‐line antitubercular drug which plays pivotal role in tuberculosis treatment. It a prodrug that requires amide hydrolysis by mycobacterial pyrazinamidase enzyme for conversion into pyrazinoic acid (POA). POA known to target ribosomal protein S1 (RpsA), aspartate decarboxylase (PanD), and some other proteins. Spontaneous chromosomal mutations RpsA have been reported phenotypic resistance against pyrazinamide. We constructed validated 3D models of the...