Prion protein pathology in Ubiquilin 2 models of ALS.

Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. However, what role these inclusions play in pathogenesis remains unclear.

Analyzing protein posttranslational modifications using enzyme-catalyzed expressed protein ligation.

Expressed protein ligation (EPL) allows for the attachment of a synthetic peptide into the N- or C-terminus of a recombinant protein fragment to generate a site-specifically modified protein with substantial yields for biochemical and biophysical studies. In this method, multiple posttranslational modifications (PTMs) can be incorporated into a synthetic peptide containing an N-terminal Cysteine, which selectively reacts with a protein C-terminal thioester to afford an amide bond formation. However, the requirement of a Cysteine at the ligation site can limit EPL's potential applications.

Polypharmacology of some medicinal plant metabolites against SARS-CoV-2 and host targets: Molecular dynamics evaluation of NSP9 RNA binding protein.

Medicinal plants as rich sources of bioactive compounds are now being explored for drug development against COVID-19. 19 medicinal plants known to exhibit antiviral and anti-inflammatory effects were manually curated, procuring a library of 521 metabolites; this was virtually screened against NSP9, including some other viral and host targets and were evaluated for polypharmacological indications. Leads were identified via rigorous scoring thresholds and ADMET filtering.

Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer.

Background: Breast Cancer (BC), a common fatal disease and the deadliest cancer next to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy is marked by targeting the activities of some receptors such as Estrogen Receptor alpha (ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for BC is tamoxifen.

Discovery of new promising USP14 inhibitors: computational evaluation of the thumb-palm pocket.

Ubiquitin-specific protease 14 (USP14) is a member of the deubiquitinating enzymes (DUBs) involved in disrupting the ubiquitin-proteasome regulation system, responsible for the degradation of impaired and misfolded proteins, which is an essential mechanism in eukaryotic cells. The involvement of USP14 in cancer progression and neurodegenerative disorders has been reported. Thereof USP14 is a prime therapeutic target; hence, designing efficacious inhibitors against USP14 is central in curbing these conditions.

flavonoids attenuate experimental nephropathy: Involvement of pro-inflammatory genes downregulation.

Nephropathy is a serious complication comorbid with a number of life-threatening diseases such as diabetes. Flavonoids are well known cytoprotective phytochemicals. Here, nephropathy associated with streptozotocin (STZ) treatment in experimental animals was challenged by flavonoids (CoF) isolated from Experimental animals were divided into control (n = 5), STZ (40 .

Flavones scaffold of as a potential xanthine oxidase inhibitor: Induced Fit Docking and ADME studies.

Gout is a type of painful inflammation initiated by the interactions between monosodium urate crystals and connective tissue. Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine, then to uric acid. The primary treatments for gout include XO inhibitors.

Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy.

Molecular docking analysis of phyto-constituents from Cannabis sativa with pfDHFR.

Available antimalarial drugs have been associated with numerous side effects, which include skin rashes and myelo-suppression. Therefore, it is of interest to explore compounds from natural source having drug-like properties without side effect. This study focuses on the screening of compounds from against malaria dihydrofolate reductase for antimalarial properties using Glide (Schrodinger maestro 2018-1).

Molecular Docking and 3D Qsar Studies of C000000956 as a Potent Inhibitor of Bace-1.

Background: BACE-1 is an aspartate protease that is responsible for the proteolysis of amyloid precursor proteins (APP) into beta-amyloid (Aβ), a neurotoxic peptide in patients with Alzheimer's disease (AD). As such, BACE-1 is a prime pharmacological target in the control of Aβ in the brain and its inhibition will be a sound approach in AD therapy.

Methods: The computational pipeline which comprised molecular docking (MD), Quantitative Structure Activity Relationship (QSAR) modelling and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies enabled the prediction of molecular interaction and relative inhibitory potentials of the hit compound.

T-705-modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA-binding pocket.

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA-approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is an emerging alternative drug with proven anti-Lassa virus activity in experimental model.

flavanones; apposite inverse agonists of the β2-adrenergic receptor in asthma treatment.

Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs.