Structure and dynamics of membrane protein in SARS-CoV-2.

SARS-CoV-2 membrane (M) protein performs a variety of critical functions in virus infection cycle. However, the expression and purification of membrane protein structure is difficult despite tremendous progress. In this study, the 3 D structure is modeled followed by intensive validation and molecular dynamics simulation.

Antiviral Peptides as Promising Therapeutics against SARS-CoV-2.

Over 50 peptides, which were known to inhibit SARS-CoV-1, were computationally screened against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Based on the binding affinity and interaction, 15 peptides were selected, which showed higher affinity compared to the α-helix of the human ACE2 receptor. Molecular dynamics simulation demonstrated that two peptides, S2P25 and S2P26, were the most promising candidates, which could potentially block the entry of SARS-CoV-2.

Cysteine focused covalent inhibitors against the main protease of SARS-CoV-2.

In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys-His catalytic dyad, and ligands that interact with the Cys145 assumed to be an effective approach to inhibit the Mpro. In this study, approximately 1400 cysteine-focused ligands were screened to identify the best candidates that can act as potent inhibitors against Mpro.

Investigating the binding affinity, interaction, and structure-activity-relationship of 76 prescription antiviral drugs targeting RdRp and Mpro of SARS-CoV-2.

SARS-CoV-2 virus outbreak poses a major threat to humans worldwide due to its highly contagious nature. In this study, molecular docking, molecular dynamics, and structure-activity relationship are employed to assess the binding affinity and interaction of 76 prescription drugs against RNA dependent RNA polymerase (RdRp) and Main Protease (Mpro) of SARS-CoV-2. The RNA-dependent RNA polymerase is a vital enzyme of coronavirus replication/transcription complex whereas the main protease acts on the proteolysis of replicase polyproteins.

Virtual screening, molecular dynamics and structure-activity relationship studies to identify potent approved drugs for Covid-19 treatment.

Computer-aided drug screening by molecular docking, molecular dynamics (MD) and structural-activity relationship (SAR) can offer an efficient approach to identify promising drug repurposing candidates for COVID-19 treatment. In this study, computational screening is performed by molecular docking of 1615 Food and Drug Administration (FDA) approved drugs against the main protease (Mpro) of SARS-CoV-2. Several promising approved drugs, including Simeprevir, Ergotamine, Bromocriptine and Tadalafil, stand out as the best candidates based on their binding energy, fitting score and noncovalent interactions at the binding sites of the receptor.

A molecular modeling approach to identify effective antiviral phytochemicals against the main protease of SARS-CoV-2.

The main protease of SARS-CoV-2 is one of the important targets to design and develop antiviral drugs. In this study, we have selected 40 antiviral phytochemicals to find out the best candidates which can act as potent inhibitors against the main protease. Molecular docking is performed using AutoDock Vina and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the main protease.

Virtual screening, molecular dynamics, density functional theory and quantitative structure activity relationship studies to design peroxisome proliferator-activated receptor-γ agonists as anti-diabetic drugs.

Type 2 diabetes (T2D) is generally characterized by elevated blood glucose levels, insulin resistance, and relative lack of insulin; however, insulin resistance is the predominant risk factor. Hence, the use of insulin sensitizer drugs to increase insulin sensitivity has gained immense interest as an attractive treatment option for T2D and their major target is a nuclear receptor PPAR-γ (peroxisome proliferator-activated receptor-γ). A wide range of synthetic insulin sensitizers such as thiazolidinedione act as PPAR-γ agonists thereby enhancing insulin action and improving hyperglycemia in patients.

Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation.

Serine-threonine kinase11 (STK11) is a tumor suppressor gene which plays a key role in regulating cell growth and apoptosis. It is widely known as a multitasking kinase and engaged in cell polarity, cell cycle arrest, chromatin remodeling, energy metabolism, and Wnt signaling. The substitutions of single amino acids in highly conserved regions of the STK11 protein are associated with Peutz-Jeghers syndrome (PJS), which is an autosomal dominant inherited disorder.

Cytotoxic and anti-inflammatory resorcinol and alkylbenzoquinone derivatives from the leaves of Ardisia sieboldii.

Medicinal plants belonging to the genus Ardisia are traditionally used to cure various human diseases including inflammation and cancer. This study aimed to purify and characterize cytotoxic and anti-inflammatory compounds from Ardisia sieboldii leaves. Bioassay-guided chromatographic analyses yielded three compounds, 2-methyl-5-(8Z-heptadecenyl) resorcinol (1), 5-(8Z-heptadecenyl) resorcinol (2), and ardisiaquinone A (3), whereas liquid chromatography-electrospray ionisation-mass spectrometry chemical profiling revealed the presence of diverse resorcinol and alkylbenzoquinone derivatives in cytotoxic 70% methanol extracts.

Halogenated derivatives of methotrexate as human dihydrofolate reductase inhibitors in cancer chemotherapy.

Methotrexate is a widely used anti-metabolite in cancer chemotherapy. A series of halogenated drugs is designed from Methotrexate to assess their interactions with human dihydrofolate reductase. The aim of this study is to evaluate the performance of the modified drugs compared to the parent Methotrexate.

Mutation Spectrum in TPO Gene of Bangladeshi Patients with Thyroid Dyshormonogenesis and Analysis of the Effects of Different Mutations on the Structural Features and Functions of TPO Protein through Approach.

Although thyroid dyshormonogenesis (TDH) accounts for 10-20% of congenital hypothyroidism (CH), the molecular etiology of TDH is unknown in Bangladesh. Thyroid peroxidase (TPO) is most frequently associated with TDH and the present study investigated the spectrum of TPO mutations in Bangladeshi patients and analyzed the effects of mutations on TPO protein structure through approach. Sequencing-based analysis of TPO gene revealed four mutations in 36 diagnosed patients with TDH including three nonsynonymous mutations, namely, p.

Aggregation behavior of cetyldimethylethylammonium bromide under the influence of bovine serum albumin in aqueous/electrolyte solutions at various temperatures and compositions: conductivity and molecular dynamics study.

Herein, we have investigated the interaction of bovine serum albumin (BSA), the most abundant globular protein, with a conventional cationic surfactant, cetyldimethylethylammonium bromide (CDMEAB), through a conductivity technique in the absence/presence of electrolyte solutions at various temperatures (298.15-323.15 K).

Metal based donepezil analogues designed to inhibit human acetylcholinesterase for Alzheimer's disease.

Among neurodegenerative disorders, Alzheimer's disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT).

Molecular docking and dynamics of Nickel-Schiff base complexes for inhibiting β-lactamase of .

In recent years, multidrug-resistance has become a primary concern in the treatment and management of tuberculosis, an infectious disease caused by . In this context, searching new anti-tuberculosis agents particularly targeting the β-lactamase (BlaC) is reported to be promising as this enzyme is one of the key player in the development of multidrug resistance. This study reports the design of some Nickel (Ni) based tetradentate NO Schiff bases, employing density functional theory.

Anti-Inflammatory, Anti-Diabetic, and Anti-Alzheimer's Effects of Prenylated Flavonoids from Okinawa Propolis: An Investigation by Experimental and Computational Studies.

Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated flavonoids from OP, nymphaeol-A (NA), nymphaeol-B (NB), nymphaeol-C (NC), isonymphaeol-B (INB), and 3'-geranyl-naringenin (GN), were evaluated for their anti-inflammatory, anti-diabetic, and anti-Alzheimer's effects using in vitro techniques. They showed significant anti-inflammatory effects through inhibition of albumin denaturation (half maximal inhibitory concentration (IC) values of 0.

Cytotoxic Desulfated Saponin from Predicted to Have High Binding Affinity to the Oncogenic Kinase PAK1: A Combined In Vitro and In Silico Study.

Sea cucumbers have long been utilized in foods and Asiatic folk medicines for their nutritive and health benefits. Herein, three sea cucumber species were investigated and showed the highest cytotoxicity among these. Next, a desulfated saponin, desulfated echinoside B (DEB), was purified from through bioassay-guided fractionation.