Biology subjects

Parvez, M. S. A.

Publications and source records attributed to Parvez, M. S. A..

7 recordsLinked to original sources

bioRxiv2023

Small Molecule Inhibitors Targeting Methyltransferase-Like (METTL) Proteins Against Hepatocellular Carcinoma: A Comprehensive DrugRepurposing Approach

An efficient and durable multi-targeted therapeutic drug against hepatocellular carcinoma (HCC) has recently been a growing concern for tackling the chemoresistance of approved anti-HCC drugs. Recent studies indicated that methyltransferase-like (METTL) proteins including METTL1, METTL3, METTL6, METTL16, and METTL18, have overexpressed and associated with the progression of HCC malignancy, and making them excellent biomarkers. Here, we present a series of bioinformatics study including novel compound repurposing approach, molecular docking, pharmacophore modeling, and molecular dynamic simulation, which revealed two first-in-class highly potent catalytic multi-target inhibitors (ZINC70666503 and ZINC13000658 with 87% and 82% drug scores, respectively) of methyltransferase-like proteins. Comparatively, these two inhibitors showed a notable binding affinity against studied METTL proteins. Furthermore, ADME and toxicity analysis suggested that these two commercially available compounds have good drug-likeliness properties with no potent toxic effects. Of note, the molecular dynamics study supported their conformational stability and high selectivity at the pocket of proteins adenosine moiety of S-Adenosyl Methionine. However, this comprehensive analysis needs in vivo validation to facilitate multi-targeting therapeutic development against hepatocellular carcinoma.

cancer biology↗

bioRxiv2021

High permeability of the CSF flow in the juvenile mouse brain by brain-wide DCE-MRI

The vasculature system with a lymphatic function in the brain is manifested as meningeal lymphatic vessels and the glymphatic system, which drain waste products from cerebrospinal fluid (CSF) and produce interstitial fluid. Invasion of stimulated immune cells or inflammatory cytokines during the maturation is regarded as a sign of the disruption of brain functions through excessive immune stresses. However, it is unclear when the lymphatic system is functionally completed and in which parts of the organ the brain immunity is privileged (i.e., the blood-brain barrier is fully established). Here, we visualized the whole-head signal of gadolinium (Gd) contrast agents in mouse brains to investigate the CSF flow from the signals of Gd-contrast agents using magnetic resonance imaging (MRI) in the course of developmental stages. We found higher Gd-signals in the olfactory bulbs, prefrontal cortex, parietal surface regions of the neocortex along with dorsal meningeal lymphatic vessels, ventral midbrain, and a part of cerebellum, as well as in the basal brain regions, at the immature stage of postnatal (P) 4 weeks, compared to the P8-12 weeks. Our results suggest that the barrier of the vasculature system in mouse brains is still permeable until P1-month and small molecules can leak into the parenchyma.

neuroscience↗

bioRxiv2021

Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems

Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF- production. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.

plant biology↗

bioRxiv2020

Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism

As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.

genomics↗

bioRxiv2020

Novel insights into the structure and transport mechanisms of TAPT1

Transmembrane anterior-posterior transformation protein 1 (TAPT1), encoded by the TAPT1 gene expressed in the basal ciliary body, plays a crucial role in cilia formation as well as axial skeletal patterning. Mutations in this gene have been reported to cause several ciliopathies and osteo-related diseases. Unfortunately, the cellular and molecular pathogenic mechanisms are still unclear also due to the lack of X-ray crystallographic structure and further characterization of TAPT1 protein. In this study, we attempted to characterize this protein by in silico techniques. A 3D structure of TAPT1 was generated by the ab initio method, which was further used for the analysis of the substrate-binding site, to determine pore size and for the prediction of the possible substrate(s). Validation by using different software packages revealed a reliable 3D model of TAPT1. Topology modeling revealed that TAPT1 has eight transmembrane helices with a total number of 27 helices in secondary structure. The amino acid residues H235, R323, K443, N446, S447, L450, K453, S454, Y457, K511, N513, D533, K535, D536, and T538 were found to form the pore surface as well as involved in the binding interaction with the substrate(s). This study predicted flavonoids as the possible substrate for TAPT1, which could further be confirmed by ingenuity pathway analysis. Moreover, our analysis indicated that TAPT1 might localize in the mitochondrial membrane in addition to the ciliary basal body. Our study gives novel insights for TAPT1 structure and its function.

biochemistry↗

bioRxiv2020

Identifying Novel Drug and Vaccine Molecules of Vibrio parahaemolyticus by Subtractive Proteomics and Vaccinomics Approach

Multidrug-resistant Vibrio parahaemolyticus has become a significant threat to human health as well as aquaculture, prioritizing the development of effective drug and vaccine candidates. Hence, the study was designed to identify novel therapeutics using a comprehensive genome-based analysis of V. parahaemolyticus. From V. parahaemolyticus proteome, a total of 4822 proteins were investigated in order to find out effective drug and vaccine targets. A range of diverse subtractive proteomics approaches - namely, identification of human non-homologous and pathogen-specific essential proteins, druggability and anti-target analysis, prediction of subcellular localization, human microbiome non-homology screening, analysis of virulence factors, protein-protein interactions studies. Among 16 novel cytoplasmic proteins, VIBPA Type II secretion system protein L and VIBPA Putative fimbrial protein Z were allowed to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, Sensor histidine protein kinase UhpB and Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T and B cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking were adopted to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules that suggested the superiority of construct V1. Besides, the binding affinity of human TLR1/2 heterodimer and construct V1 was also biologically significant. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied to combat V. parahaemolyticus associated infections.

microbiology↗

bioRxiv2020

Scrutinizing surface glycoproteins and poxin-schlafen protein to design a heterologous recombinant vaccine against monkeypox virus

Monkeypox is a zoonotic disease caused by monkeypox virus with noteworthy mortality and morbidity. Several recent outbreaks and the need of dependable reconnaissance have raised the level of concern for this developing zoonosis. In the present study, a reverse vaccinology strategy was developed to construct a peptide vaccine against monkeypox virus by exploring cell surface binding protein, Poxin-Schlafen andenvelope protein. Both humoral and cell mediated immunity induction were the main concerned properties for the designed peptide vaccine. Therefore, both T cell and B cell immunity against monkeypox virus were analyzed from the conserver region of the selected protein. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were used to create the superior epitopes of moneypox virus. The subunit vaccine was constructed using highly immunogenic epitopes with appropriate adjuvant and linkers. Molecular docking examination of the refined vaccine with various MHCs and human immune receptor illustrated higher binding interaction. The designed construct was reverse transcribed and adjusted for E. coli strain K12 earlier to inclusion inside pET28a(+) vector for its heterologous cloning and expression. The study could start in vitro and in vivo studies concerning effective vaccine development against monkeypox virus.

bioinformatics↗