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This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation.

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Background: Chronic kidney disease (CKD), is a major public health challenge worldwide. It is more prevalent in developed countries compared with the rest of the world, due to the higher rates of life expectancy and unhealthy lifestyle related factors. This aim of the current study is to evaluate the relationship between interleukins IL-2 and IL-17 concentrations and kidney function markers in men with CKD. Methods: Forty-five men with CKD and seventy controls were enrolled in the current study to assess the relationship between interleukin-2 (IL-2), interleukin-17 (IL-17), and CKD parameters. Fasting blood samples were collected from patients with CKD and their controls at same time. Serum IL-2, and IL-17 were measured in patients with CKD and their controls, and then the relationship between these interleukins and serum creatinine, serum urea, serum uric acid and urine albumin were evaluated. Results: A significant relationship was detected between IL-2 (p< 0.001), IL-17 (p< 0.001) levels and serum creatinine concentrations. The significant increase of IL-2 and IL-17 levels were also paralleled with a significant increase in serum urea (p< 0.001), and urine albumin (p< 0.001) concentrations respectively. Conclusions: IL-2 and IL-17 may play a critical role in the pathophysiology of CKD. The significant increase of IL-2 and IL-17 is associated with significantly high concentrations of creatinine, serum urea and urine albumin suggesting that these interleukins may be used as targets for future biomarkers and molecular therapy. However, due to limited sample size of the current study, larger prospective cohorts are needed to confirm these observations.

Thyroid hormones (THs) have a significant effect on the cardiovascular system. THs increase myocardium stretch, leading to the release of B-type Natriuretic Peptide (BNP), which is considered a diagnostic biomarker of heart failure (HF). Thyroid dysfunctions (subclinical hypothyroidism; SCH and subclinical hyperthyroidism; SCHyper) stimulate several changes in the heart by causing either diastolic or systolic left ventricular dysfunctions leading to HF. This study aims to measure the changes of B- type NP levels in cases of subclinical hypo and hyperthyroidism. The present study aims to measure the changes in B-type Natriuretic Peptide (BNP) levels in subclinical hypo and hyperthyroidism (SCH and SCHyper). A theoretical study was also conducted using a docking program to find the effectiveness of some drugs in inhibiting or promoting B-type Natriuretic Peptide (BNP). A case study was conducted in a private clinic, Mosul- Iraq, from (April 1st – Sep 1) 2021, with 25 healthy participants with normal functioning thyroids as a control group (EU). A newly diagnosed 25 SCH and 17 SCHyper patients participated in this study, considering that none of them have thyroid dysfunctions taking medicine, hypertension, heart diseases, renal failure, and pregnant women. They all were checked for Thyroid Function Tests (TFTs), Free Triiodothyronine (FT3), Free Thyroxin (FT4) and Thyroid Stimulating Hormone (TSH). The plasma level of BNP was measured in all participants of the three groups. The results showed that the plasma level of BNP was higher in SCHyper patients (10.97 pg/ml) as compared to that of SCH patients (8.09 pg/ml) and EU subjects (8.27 pg/ml). Hereby, we could state that subclinical hyperthyroidism, SCHyper, triggers BNP release. Therefore, it should be kept in mind that any high BNP levels due to SCHyper should be considered a reliable diagnostic biomarker of heart failure (HF). Keywords. Thyroid hormone(TH), Subclinical hypothyroidism(SCH), Subclinical hyperthyroidism(SCHyper), Chronic heart disease(CHD), Heart failure(HF), B-type natriuretic peptide(BNP), Docking Study.