Exploring the phytomedicine properties of azadiradione against leishmaniasis: in silico and in vitro insights.

Background: Leishmaniasis continues to pose a significant global health challenge, exacerbated by the increasing resistance to current therapeutic agents such as miltefosine and amphotericin B. This growing resistance highlights the urgent need for alternative treatment strategies. In this context, phytomedicine has emerged as a promising avenue for novel antileishmanial therapies.

Unearthing novel mutations and genetic variation in drug sensitive and resistant isolates of Mycobacterium tuberculosis through whole genome sequencing: A study from eastern Uttar Pradesh, India.

Purpose: Drug-resistant tuberculosis (DR-TB) presents a formidable public health challenge worldwide. Therefore, this study was conducted to elucidate the complete genetic profiles of drug-sensitive (DS), and drug-resistant TB isolates using Whole Genome Sequencing (WGS).

Methods: The study includes a set of sputum specimens containing five DS-TB, multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) from distinct individuals.

Harnessing computational methods for uncovering structural insights into 3-MST: implications for drug design and target specificity.

Unlabelled: 3-Mercaptopyruvate sulfurtransferase (3-MST) is an enzyme that plays integral roles in various biological processes. In the realm of , the role of 3-MST is less explored. It is a critical player in maintaining oxidative homeostasis in during stress for survival.

A review of non-invasive samples and tools in kala-azar diagnosis and test of cure.

The recurrence of visceral leishmaniasis (VL), also called kala-azar (KA), in endemic regions of tropical countries like India, is primarily attributed to asymptomatic VL, post-kala azar dermal leishmaniasis (PKDL), and human immunodeficiency virus (HIV) co-infection. To effectively manage VL cases and elimination targets, an early and rapid diagnosis as well as accurate field surveillance is highly essential. The traditional sampling methods like bone marrow (BM), spleen, and lymph node (LN) tissue aspirations are invasive, painful, tedious, and prone to nosocomial infections, require skilled persons and hospital facilities, and are not feasible in rural areas.

The Application of MD Simulation to Lead Identification, Vaccine Design, and Structural Studies in Combat against Leishmaniasis - A Review.

Drug discovery, vaccine design, and protein interaction studies are rapidly moving toward the routine use of molecular dynamics simulations (MDS) and related methods. As a result of MDS, it is possible to gain insights into the dynamics and function of identified drug targets, antibody-antigen interactions, potential vaccine candidates, intrinsically disordered proteins, and essential proteins. The MDS appears to be used in all possible ways in combating diseases such as cancer, however, it has not been well documented as to how effectively it is applied to infectious diseases such as Leishmaniasis.

In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase.

In Leishmania sp., the enzymes of de novo cysteine biosynthesis pathway require sulfide. Other organisms utilize sulfide through the sulfide reduction pathway, but Leishmania lacks the gene that encodes these enzymes.

Harnessing Fuzzy Rule Based System for Screening Major Histocompatibility Complex Class I Peptide Epitopes from the Whole Proteome: An Implementation on the Proteome of .

The development of peptide-based vaccines is enhanced by immunoinformatics, which predicts the patterns that B cells and T cells recognize. Although several tools are available for predicting the Major histocompatibility complex (MHC-I) binding peptides, the wide variants of human leucocyte antigen allele make it challenging to choose a peptide that will induce an immune response in a majority of people. In addition, for a peptide to be considered a potential vaccine candidate, factors such as T cell affinity, proteasome cleavage, and similarity to human proteins also play a major role.

Differential translational regulation of host exosomal proteins play key role in immunomodulation in antimony resistance in Visceral Leishmaniasis: A proteomic profiling study.

In host-pathogen interactions, exosomal secretions are crucial for cell to cell communication and have an established role in immunomodulation. Protozoans, including Leishmania, modulates their host vesicular secretions for better survival; although the role of exosomal secretions in unresponsive against sodium antimony gluconate (SAG) has never been documented. In this study, the exosomal proteome of RAW macrophages infected with either SAG responsive (SAG) or SAG unresponsive (SAG) L.

Exploring nod factor receptors activation process in chickpea by bridging modelling, docking and molecular dynamics simulations.

Plasma membrane-bound receptor proteins play crucial roles in the perception and further transmission of regulatory signals to modulate numerous developmental and metabolic events. Precise functioning and fine-tuning of Nod factor receptor (NFR) mediated signalling is a critical requirement for root nodule symbiosis. Here, we have identified, cloned and phylogenetically characterized chickpea NFR1 and NFR5, which are showing significant homology with other legume NFR receptors.

Differentially modulated proteins associated with Leishmaniasis-a systematic review of in-vivo and in-vitro studies.

High-throughput proteomic technologies are widely used for understanding the disease mechanism, drug-resistant mechanism, and to identify drug targets and markers for diagnostics. Studies with proteomics applications, relating to Leishmaniasis, are being constantly reported in the literature. However, from such studies, a readily accessible knowledge of differentially modulated proteins associated with Leishmaniasis is lacking.

and analysis of enoyl acyl carrier protein reductase - A possible drug target.

The emergence of increased resistance to the available drugs has created a situation that demands to find out more specific molecular drug targets for Leishmaniasis. The enoyl acyl carrier protein reductase (ENR), a regulatory enzyme in type II fatty acid synthesis, was confirmed as a novel drug target and triclosan as its specific inhibitor in many microorganisms. In this study, the triclosan was tested for the leishmanicidal property against () and the results of and drug assays on promastigotes and amastigotes showed that triclosan possessed antileishmanial activity with a half minimal inhibitory concentration (IC) of 30 µM.

TrypInDB: A searchable online resource of small molecule inhibitors against Trypanosoma sp.

African Trypanosomiasis and American Trypanosomiasis are the diseases affecting more than thousands of people yearly and more than twenty-five million people risk acquiring the disease. The treatment for the disease is generally expensive, and most of the available drugs are of high-toxicity and cause fatal side-effects. Hence, there is a constant need for finding new treatment strategies for Trypanosomiasis.

Leishmania donovani infection induce differential miRNA expression in CD4+ T cells.

Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host upon Leishmania infection. However, the regulatory mechanism for Th1/2 production is not well understood.

LeishInDB: A web-accessible resource for small molecule inhibitors against Leishmania sp.

Despite the availability of drugs to treat Leishmaniasis, various other factors including drug resistance and adverse side effects encourage the researchers to search for new strategies and alternatives for treating Leishmaniasis. Repurposing and devising combination therapy with the existing small molecules would serve as an alternative strategy to address the issue, especially the drug resistance. Hence, here we report LeishInDB, a web-accessible resource of small molecule inhibitors having a varying degree of activity towards Leishmania sp.

Validation of NAD synthase inhibitors for inhibiting the cell viability of : and approach.

NAD (nicotinamide adenine dinucleotide) synthase catalyses the biochemical synthesis of NAD, from nicotinic acid adenine dinucleotide (NAAD). NAD may be synthesized through the pathways and/or the salvage pathways in cells. However, in parasite, the synthesis of NAD solely depends on the salvage pathways.

Exploring microRNAs, Target mRNAs and their Functions in Leguminous Plant .

Background: MicroRNAs (miRNAs) are a class of small non-coding, endogenous RNAs that regulate gene expression at post-transcriptional level. In plants, miRNAs are usually of 18-24 nucleotide in length and play humongous role by aiding in development, growth, defense, biotic and abiotic stress responses, etc. Objective: Arachis hypogaea is an economically important oil seed crop and human dietary source cultivated mostly in tropical and subtropical regions.

Structural, molecular motions, and free-energy landscape of Leishmania sterol-14α-demethylase wild type and drug resistant mutant: a comparative molecular dynamics study.

Sterol-14α-demethylase (CYP51) is an ergosterol pathway enzyme crucial for the survival of infectious Leishmania parasite. Recent high-throughput metabolomics and whole genome sequencing study revealed amphotericin B resistance in Leishmania is indeed due to mutation in CYP51. The residue of mutation (asparagine 176) is conserved across the kinetoplastidae and not in yeast or humans, portraying its functional significance.

Recent progress in drug targets and inhibitors towards combating leishmaniasis.

Lesihmaniasis is one of the major neglected tropical disease caused by the parasite of the genus Leishmania. The disease has more than one clinical forms and the visceral form is considered fatal. With the lack of potential vaccine, chemotherapy is the major treatment source considered for the control of the disease in the infected people.

In-silico screening and validation of high-affinity tetra-peptide inhibitor of Leishmania donovani O-acetyl serine sulfhydrylase (OASS).

OASS is a specific enzyme that helps Leishmania parasite to survive the oxidative stress condition in human macrophages. SAT C-terminal peptides in several organisms, including Leishmania, were reported to inhibit or reduce the activity of OASS. Small peptide and small molecules mimicking the SAT C-terminal residues are designed and tested for the inhibition of OASS in different organisms.

Mammalian Mitochondrial ncRNA Database.

Unlabelled: Mammalian Mitochondrial ncRNA is a web-based database, which provides specific information on non-coding RNA in mammals. This database includes easy searching, comparing with BLAST and retrieving information on predicted structure and its function about mammalian ncRNAs.

Availability: The database is available for free at http://www.

Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor.

Proteins embody epitopes that serve as their antigenic determinants. Epitopes occupy a central place in integrative biology, not to mention as targets for novel vaccine, pharmaceutical, and systems diagnostics development. The presence of T-cell and B-cell epitopes has been extensively studied due to their potential in synthetic vaccine design.

Allosteric site-mediated active site inhibition of PBP2a using Quercetin 3-O-rutinoside and its combination.

Recent crystallographic study revealed the involvement of allosteric site in active site inhibition of penicillin binding protein (PBP2a), where one molecule of Ceftaroline (Cef) binds to the allosteric site of PBP2a and paved way for the other molecule (Cef) to bind at the active site. Though Cef has the potency to inhibit the PBP2a, its adverse side effects are of major concern. Previous studies have reported the antibacterial property of Quercetin derivatives, a group of natural compounds.

Quercetin 3-O-rutinoside mediated inhibition of PBP2a: computational and experimental evidence to its anti-MRSA activity.

The PBP2a is a cell wall synthesizing protein, which causes resistivity in methicillin resistant Staphylococcus aureus (MRSA) from β-lactam antibiotics but it is susceptible to 5th generation cephalosporin, ceftobiprole. Ceftobiprole inhibits the growth of MRSA by targeting the PBP2a-mediated cell wall synthesis, but it is reported to have adverse side effects. Due to this, there is a constant need to develop natural alternatives, which are generally free from adverse side effects.

Fuzzy logic for personalized healthcare and diagnostics: FuzzyApp--a fuzzy logic based allergen-protein predictor.

The path to personalized medicine demands the use of new and customized biopharmaceutical products containing modified proteins. Hence, assessment of these products for allergenicity becomes mandatory before they are introduced as therapeutics. Despite the availability of different tools to predict the allergenicity of proteins, it remains challenging to predict the allergens and nonallergens, when they share significant sequence similarity with known nonallergens and allergens, respectively.

APSLAP: an adaptive boosting technique for predicting subcellular localization of apoptosis protein.

Apoptotic proteins play key roles in understanding the mechanism of programmed cell death. Knowledge about the subcellular localization of apoptotic protein is constructive in understanding the mechanism of programmed cell death, determining the functional characterization of the protein, screening candidates in drug design, and selecting protein for relevant studies. It is also proclaimed that the information required for determining the subcellular localization of protein resides in their corresponding amino acid sequence.