Publications by authors named "M S Alamri"

117 Publications

Structural Elucidation of Rift Valley Fever Virus L Protein towards the Discovery of Its Potential Inhibitors.

Pharmaceuticals (Basel) 2022 May 25;15(6). Epub 2022 May 25.

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.

Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants. Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans. The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no effective and specific vaccine against this virus is available. The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet. The inhibitory binding modes of known potent L protein inhibitors were analyzed. Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed. Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations. Homology modeling determined a stable multi-domain structure of L protein. An analysis of known L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket. The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket. ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds. Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein. In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.
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http://dx.doi.org/10.3390/ph15060659DOI Listing
May 2022

Severe Rheumatic Mitral Stenosis, Worse Left Atrial Mechanics is Closely Associated with Echo Criteria for Intervention.

J Cardiovasc Echogr 2022 Jan-Mar;32(1):38-46. Epub 2022 Apr 20.

University of Glasgow, Adult Congenital Cardiac Service, Glasgow, Scotland.

Background: Rheumatic mitral valve (MV) stenosis is associated with progressive left atrial (LA) fibrosis and functional impairment, Pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction. The aims of the study were to determine in those patients with severe MV stenosis if LA mechanical function as assessed by speckle tracking echocardiography could identify those with increased PASP, atrial fibrillation (AFib), and RV dysfunction.

Subjects And Methods: Patients with severe MV stenosis were identified from the institutional echo database. Echocardiograms were read off line and measurements included atrial and ventricular strain. Patients were divided into tertiles of LA reservoir strain (LASr) values and data compared between the groups.

Results: Ninety-seven patients, 67 females, mean age 47.4 ± 11.9 years, had MV mean gradient of 8.3 ± 5.1 mmHg, MV area by pressure half time of 1.3 ± 0.3 cm and LASr of 11.18% ± 6.4%. Those patients in the lowest LASr tertile had more AFib (72%, = 0.0001), PASP >50 mm Hg (39%, = 0.005), and worst RV impairment. In multivariable logistic regression analysis, LASr, age, and mean MV gradient were the independent predictors of AFib and PASP >50 mm Hg. Cutoffs, determined by receiver operating characteristic curve analysis had high specificity for the composite outcome of Afib and PASP >50 mmHg (85% for LASr <7.7%).

Conclusion: In severe MV stenosis LASr, age and mean MV gradient, are independent predictors of Afib and PASP >50 mmHg. LASr <7.7% has high sensitivity and specificity in identifying those who meet ESC guideline 2017 criteria for valve intervention, suggesting its potentially helpful addendum to the surveillance of patients with MV stenosis.
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http://dx.doi.org/10.4103/jcecho.jcecho_80_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164921PMC
April 2022

Discovery of Rift Valley fever virus natural pan-inhibitors by targeting its multiple key proteins through computational approaches.

Sci Rep 2022 Jun 3;12(1):9260. Epub 2022 Jun 3.

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia.

The Rift Valley fever virus (RVFV) is a zoonotic arbovirus and pathogenic to both humans and animals. Currently, no proven effective RVFV drugs or licensed vaccine are available for human or animal use. Hence, there is an urgent need to develop effective treatment options to control this viral infection. RVFV glycoprotein N (GN), glycoprotein C (GC), and nucleocapsid (N) proteins are attractive antiviral drug targets due to their critical roles in RVFV replication. In present study, an integrated docking-based virtual screening of more than 6000 phytochemicals with known antiviral activities against these conserved RVFV proteins was conducted. The top five hit compounds, calyxin C, calyxin D, calyxin J, gericudranins A, and blepharocalyxin C displayed optimal binding against all three target proteins. Moreover, multiple parameters from the molecular dynamics (MD) simulations and MM/GBSA analysis confirmed the stability of protein-ligand complexes and revealed that these compounds may act as potential pan-inhibitors of RVFV replication. Our computational analyses may contribute toward the development of promising effective drugs against RVFV infection.
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http://dx.doi.org/10.1038/s41598-022-13267-1DOI Listing
June 2022

Effect of Ziziphus and Cordia Gums on Dough Properties and Baking Performance of Cookies.

Molecules 2022 May 10;27(10). Epub 2022 May 10.

Department of Food Science and Nutrition, King Saud University, Riyadh 1145, Saudi Arabia.

The influence of 2% and 5% Cordia (CG) and Ziziphus (ZG) gums on dough characteristics and cookie quality was investigated. Micro-DoughLab, a texture analyzer (TA), a rapid viscoanalyzer (RVA), and solvent retention capacity were used to examine the effect of CG and ZG gums on dough physicochemical parameters (SRC) and cookie quality. The diameter, thickness, spread, and sensory evaluation of cookies were evaluated. With the addition of CG and ZG, dough softness, mixing time, and mixing tolerance index (MTI) increased, whereas stability and water absorption decreased. TA data showed that adding gums resulted in softer and less sticky doughs than the control, whereas RVA data showed that adding CG resulted in a significant increase in peak viscosity, but no change in flour gel setback. In comparison to the control and CG samples, the ZG samples exhibited the most dough extensibility. The thickness and diameter of the cookies increased but the spread decreased, due to the added gums. The gum-containing cookies had a lower overall acceptability by panelists than the control, although only by a small margin. Gum-containing cookies, on the other hand, can deliver up to 5% soluble fiber.
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http://dx.doi.org/10.3390/molecules27103066DOI Listing
May 2022

Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study.

J Pers Med 2022 May 1;12(5). Epub 2022 May 1.

Department of Family medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.

Background: Sedentary lifestyles, urbanization and improvements in socio-economic status have had serious effects on the burden of diabetes across the world. Diabetes is one of the 10 leading causes of death globally, and individuals with diabetes have a 2-3-fold increased risk of all-cause mortality. Adipose tissue is increasingly understood as a highly active endocrine gland that secretes many biologically active substances, including adipocytokines. However, the exact and discrete pathophysiological links between obesity and T2DM are not yet fully elucidated.

Methods: In the current study, we present the association of five diverse adipocytokines, adiponectin, leptin, resistin, visfatin and chemerin, with T2DM in 87 patients (46 males and 41 females) with type 2 diabetes mellitus and 85 healthy controls (44 males and 41 females) from the Asir region of Saudi Arabia. The patients were divided into four groups: normal BMI, overweight, obese and severely obese. The baseline biochemical characteristics, including HbA1c and anthropometric lipid indices, such as BMI and waist-hip ratio, were determined by standard procedures, whereas the selected adipokine levels were assayed by ELISA.

Results: The results showed significantly decreased levels of adiponectin in the T2DM patients compared to the control group, and the decrease was more pronounced in obese and severely obese T2DM patients. Serum leptin levels were significantly higher in the females compared to the males in the controls as well as all the four groups of T2DM patients. In the male T2DM patients, a progressive increase was observed in the leptin levels as the BMI increased, although these only reached significantly altered levels in the obese and severely obese patients. The serum leptin levels were significantly higher in the severely obese female patients compared to the controls, patients with normal BMI, and overweight patients. The leptin/adiponectin ratio was significantly higher in the obese and severely obese patients compared to the controls, patients with normal BMI, and overweight patients in both genders. The serum resistin levels did not show any significant differences between the males and females in thr controls or in the T2DM groups, irrespective of the BMI status of the T2DM patients. The visfatin levels did not reveal any significant gender-based differences, but significantly higher levels of visfatin were observed in the T2DM patients, irrespective of their level of obesity, although the higher values were observed in the obese and highly obese patients. Similarly, the serum chemerin levels in the controls, as well as in T2DM patients, did not show any significant gender-based differences. However, in the T2DM patients, the chemerin levels showed a progressive increase, with the increase in BMI reaching highly significant levels in the obese and severely obese patients, respectively.

Conclusion: In summary, it is concluded that significantly altered concentrations of four adipokines, adiponectin, leptin, visfatin and chemerin, were found in the T2DM patient group compared to the controls, with more pronounced alterations observed in the obese and highly obese patients. Thus, it can be surmised that these four adipokines play a profound role in the onset, progression and associated complications of T2DM. In view of the relatively small sample size in our study, future prospective studies are needed on a large sample size to explore the in-depth relationship between adipokines and T2DM.
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http://dx.doi.org/10.3390/jpm12050735DOI Listing
May 2022
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