asmae saih

To assess the effect of missense variants and the degree of pathogenicity of each nsSNP on the function, structure, and stability of the glucokinase protein (GCK), several algorithms were utilized including PHD-SNP, PROVEAN, SNPs&GO, PolyPhen 2.0, SIFT, MutPred, I-Mutant, MUpro, Consurf, and STRING. We have evaluated the flexibility levels of the residues in GCK protein using PredFlexy server and then we used the DynOmics server to study the molecular dynamics and understand the correlated communications between the residues.Towards the end, TM-align and the PyMol program were used to analyze the topology and structural similarity between the native model and the generated mutants.In total, seven out of eight nsSNPs were fund to be the most damaging variants and to exhibit a deleterious effect on the structure of the GCK protein, and probably on its function. This in silico study gives information on functional polymorphisms that impact the structure, stability, and function of the GCK protein, and consequently susceptibility to Gestational Diabetes.

The SARS-CoV-2 is the novel coronavirus that causes the pandemic COVID-19, which has originated in Wuhan, China, in December 2019. Early studies have generally shown that human Angiotensin-Converting Enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are responsible for the viral entry of SARS-CoV-2 into target cells. TMPRSS2 as androgen-regulated is highly expressed in the prostate and other tissues including the lung. We investigated the interaction between the TMPRSS2 protein and selected antiandrogens, namely Bicalutamide, Enzalutamide, Apalutamide, Flutamide, Nilutamide, and Darolutamide using in-silico molecular docking. The results showed that Apalutamide (-8.8 Kcal/mol) and Bicalutamide (-8.6 Kcal/mol) had the highest docking score. The molecular docking process was validated by re-docking the peptide like-inhibitor-serine protease hepsin and superimposing them onto the reference complex. Last of all, the tested compounds have been evaluated for their pharmacokinetic and drug likeness properties and concluded that these compounds except Nilutamide (mutagenic) can be granted as potential inhibitors of SARS-CoV-2. This in-silico study result encourages its use as means for drug discovery of new COVID-19 treatment.