Displaying all 20 publications

Abstract:
Sort:
  1. Ali SS, Moinuddin M, Raza K, Adil SH
    ScientificWorldJournal, 2014;2014:850189.
    PMID: 24987745 DOI: 10.1155/2014/850189
    Radial basis function neural networks are used in a variety of applications such as pattern recognition, nonlinear identification, control and time series prediction. In this paper, the learning algorithm of radial basis function neural networks is analyzed in a feedback structure. The robustness of the learning algorithm is discussed in the presence of uncertainties that might be due to noisy perturbations at the input or to modeling mismatch. An intelligent adaptation rule is developed for the learning rate of RBFNN which gives faster convergence via an estimate of error energy while giving guarantee to the l 2 stability governed by the upper bounding via small gain theorem. Simulation results are presented to support our theoretical development.
  2. Ali SS, Ahmad WANW, Budin SB, Zainalabidin S
    Rev Cardiovasc Med, 2020 Jun 30;21(2):225-240.
    PMID: 32706211 DOI: 10.31083/j.rcm.2020.02.49
    In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease.
  3. Ali SS, Arsad A, Roberts KL, Asif M
    Nanomaterials (Basel), 2023 Jan 11;13(2).
    PMID: 36678058 DOI: 10.3390/nano13020304
    The use of fluidization assistance can greatly enhance the fluidization hydrodynamics of powders that exhibit poor fluidization behavior. Compared to other assistance techniques, pulsed flow assistance is a promising technique for improving conventional fluidization because of its energy efficiency and ease of process implementation. However, the inlet flow configuration of pulsed flow can significantly affect the bed hydrodynamics. In this study, the conventional single drainage (SD) flow strategy was modified to purge the primary flow during the non-flow period of the pulse to eliminate pressure buildup in the inlet flow line while providing a second drainage path to the residual gas. The bed dynamics for both cases, namely, single drainage (SD) and modified double drainage (MDD), were carefully monitored by recording the overall and local pressure drop transients in different bed regions at two widely different pulsation frequencies of 0.05 and 0.25 Hz. The MDD strategy led to substantially faster bed dynamics and greater frictional pressure drop in lower bed regions with significantly mitigated segregation behavior. The spectral analysis of the local and global pressure transient data in the frequency domain revealed a pronounced difference between the two flow strategies. The application of the MDD inlet flow strategy eliminated the disturbances from the pulsed fluidized bed irrespective of the pulsation frequency.
  4. Fadilah N, Mohamad-Saleh J, Abdul Halim Z, Ibrahim H, Syed Ali SS
    Sensors (Basel), 2012;12(10):14179-95.
    PMID: 23202043 DOI: 10.3390/s121014179
    Ripeness classification of oil palm fresh fruit bunches (FFBs) during harvesting is important to ensure that they are harvested during optimum stage for maximum oil production. This paper presents the application of color vision for automated ripeness classification of oil palm FFB. Images of oil palm FFBs of type DxP Yangambi were collected and analyzed using digital image processing techniques. Then the color features were extracted from those images and used as the inputs for Artificial Neural Network (ANN) learning. The performance of the ANN for ripeness classification of oil palm FFB was investigated using two methods: training ANN with full features and training ANN with reduced features based on the Principal Component Analysis (PCA) data reduction technique. Results showed that compared with using full features in ANN, using the ANN trained with reduced features can improve the classification accuracy by 1.66% and is more effective in developing an automated ripeness classifier for oil palm FFB. The developed ripeness classifier can act as a sensor in determining the correct oil palm FFB ripeness category.
  5. Batra YK, Ivanova M, Ali SS, Shamsah M, Al Qattan AR, Belani KG
    Paediatr Anaesth, 2005 Dec;15(12):1094-7.
    PMID: 16324030 DOI: 10.1111/j.1460-9592.2005.01633.x
    BACKGROUND: Laryngospasm is a well-known problem typically occurring immediately following tracheal extubation. Propofol is known to inhibit airway reflexes. In this study, we sought to assess whether the empiric use of a subhypnotic dose of propofol prior to emergence will decrease the occurrence of laryngospasm following extubation in children.
    METHODS: After approval from the Institutional Ethics Committee and informed parental consent, we enrolled 120 children ASA physical status I and II, aged 3-14 years who were scheduled to undergo elective tonsillectomy with or without adenoidectomy under standard general anesthesia. Before extubation, the patients were randomized and received in a blinded fashion either propofol 0.5 mg.kg(-1) or saline (control) intravenously. Tracheal extubation was performed 60 s after administration of study drug, when the child was breathing regularly and reacting to the tracheal tube.
    RESULTS: Laryngospasm was seen in 20% (n = 12) of the 60 children in the control group and in only 6.6% (n = 4) of 60 children in the propofol group (P < 0.05).
    CONCLUSIONS: During emergence from inhalational anesthesia, propofol in a subhypnotic dose (0.5 mg.kg(-1)) decreases the likelihood of laryngospasm upon tracheal extubation in children undergoing tonsillectomy with or without adenoidectomy.
  6. Abdul Latiff L, Tajik E, Ibrahim N, Abubakar AS, Ali SS
    PMID: 27086434
    Research in the field of factors associated with depression among adolescents is lacking in Malaysia. The aims of the present study were to assess the current prevalence of depression and its related factors among secondary school students in Pasir Gudang, South Malaysia. In this cross sectional study, 2,927 secondary school students (13-17 years old) from urban areas were screened for symptoms of mental disorder as well as demographic and risk behaviors using a validated Depression, Anxiety and Stress Scale (DASS) 12 questionnaire. The majority of the respondents (53.8%) were Malay, of which 53.1% were female. Symptoms of mild depression were found in 33.2% of the respondents, while the prevalence of the symptoms of moderate, severe, and extremely severe depression was 21.5%, 18.1%, and 3.0%, respectively. Logistic regression suggested that participants who were Chinese or had a lower average grade were three times more likely to have depression, while those who came from a single-parent family were twice as likely to have this condition. This study indicated that academic performance and risk behaviors along with the demographic characteristics are important contributors to adolescent depression.
  7. Batra YK, Al Qattan AR, Ali SS, Qureshi MI, Kuriakose D, Migahed A
    Paediatr Anaesth, 2004 Jun;14(6):452-6.
    PMID: 15153205
    Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children.
  8. Ali SS, Mohamed SFA, Rozalei NH, Boon YW, Zainalabidin S
    Cardiovasc Toxicol, 2019 02;19(1):72-81.
    PMID: 30128816 DOI: 10.1007/s12012-018-9478-7
    Heart failure-associated morbidity and mortality is largely attributable to extensive and unregulated cardiac remodelling. Roselle (Hibiscus sabdariffa) calyces are enriched with natural polyphenols known for antioxidant and anti-hypertensive effects, yet its effects on early cardiac remodelling in post myocardial infarction (MI) setting are still unclear. Thus, the aim of this study was to investigate the actions of roselle extract on cardiac remodelling in rat model of MI. Male Wistar rats (200-300 g) were randomly allotted into three groups: Control, MI, and MI + Roselle. MI was induced with isoprenaline (ISO) (85 mg/kg, s.c) for two consecutive days followed by roselle treatment (100 mg/kg, orally) for 7 days. Isoprenaline administration showed changes in heart weight to body weight (HW/BW) ratio. MI was especially evident by the elevated cardiac injury marker, troponin-T, and histological observation. Upregulation of plasma levels and cardiac gene expression levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 was seen in MI rats. A relatively high percentage of fibrosis was observed in rat heart tissues with over-expression of collagen (Col)-1 and Col-3 genes following isoprenaline-induced MI. On top of that, cardiomyocyte areas were larger in heart tissues of MI rats with upregulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression, indicating cardiac hypertrophy. Interestingly, roselle supplementation attenuated elevation of plasma troponin-T, IL-6, IL10, and gene expression level of IL-10. Furthermore, reduction of cardiac fibrosis and hypertrophy were observed. In conclusion, roselle treatment was able to limit early cardiac remodelling in MI rat model by alleviating inflammation, fibrosis, and hypertrophy; hence, the potential application of roselle in early adjunctive treatment to prevent heart failure.
  9. Mumtaz W, Xia L, Mohd Yasin MA, Azhar Ali SS, Malik AS
    PLoS One, 2017;12(2):e0171409.
    PMID: 28152063 DOI: 10.1371/journal.pone.0171409
    Treatment management for Major Depressive Disorder (MDD) has been challenging. However, electroencephalogram (EEG)-based predictions of antidepressant's treatment outcome may help during antidepressant's selection and ultimately improve the quality of life for MDD patients. In this study, a machine learning (ML) method involving pretreatment EEG data was proposed to perform such predictions for Selective Serotonin Reuptake Inhibitor (SSRIs). For this purpose, the acquisition of experimental data involved 34 MDD patients and 30 healthy controls. Consequently, a feature matrix was constructed involving time-frequency decomposition of EEG data based on wavelet transform (WT) analysis, termed as EEG data matrix. However, the resultant EEG data matrix had high dimensionality. Therefore, dimension reduction was performed based on a rank-based feature selection method according to a criterion, i.e., receiver operating characteristic (ROC). As a result, the most significant features were identified and further be utilized during the training and testing of a classification model, i.e., the logistic regression (LR) classifier. Finally, the LR model was validated with 100 iterations of 10-fold cross-validation (10-CV). The classification results were compared with short-time Fourier transform (STFT) analysis, and empirical mode decompositions (EMD). The wavelet features extracted from frontal and temporal EEG data were found statistically significant. In comparison with other time-frequency approaches such as the STFT and EMD, the WT analysis has shown highest classification accuracy, i.e., accuracy = 87.5%, sensitivity = 95%, and specificity = 80%. In conclusion, significant wavelet coefficients extracted from frontal and temporal pre-treatment EEG data involving delta and theta frequency bands may predict antidepressant's treatment outcome for the MDD patients.
  10. Ali SS, Noordin L, Bakar RA, Zainalabidin S, Jubri Z, Wan Ahmad WAN
    Cardiovasc Toxicol, 2021 08;21(8):605-618.
    PMID: 34114196 DOI: 10.1007/s12012-021-09666-x
    Clinically, timely reperfusion strategies to re-establish oxygenated blood flow in ischemic heart diseases seem to salvage viable myocardium effectively. Despite the remarkable improvement in cardiac function, reperfusion therapy could paradoxically trigger hypoxic cellular injury and dysfunction. Experimental laboratory models have been developed over the years to explain better the pathophysiology of cardiac ischemia-reperfusion injury, including the in vitro hypoxia-reoxygenation cardiac injury model. Furthermore, the use of nutritional myocardial conditioning techniques have been successful. The cardioprotective potential of flavonoids have been greatly linked to its anti-oxidant, anti-apoptotic and anti-inflammatory properties. While several studies have reviewed the cardioprotective properties of flavonoids, there is a scarce evidence of their function in the hypoxia-reoxygenation injury cell culture model. Hence, the aim of this review was to lay out and summarize our current understanding of flavonoids' function in mitigating hypoxia-reoxygenation cardiac injury based on evidence from the last five years. We also discussed the possible mechanisms of flavonoids in modulating the cardioprotective effects as such information would provide invaluable insight on future therapeutic application of flavonoids.
  11. Zeb A, Ali SS, Azad AK, Safdar M, Anwar Z, Suleman M, et al.
    Comput Biol Med, 2021 06;133:104412.
    PMID: 33934066 DOI: 10.1016/j.compbiomed.2021.104412
    Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.
  12. Hameed HA, Khan S, Shahid M, Ullah R, Bari A, Ali SS, et al.
    Drug Des Devel Ther, 2020;14:27-41.
    PMID: 32021089 DOI: 10.2147/DDDT.S232111
    BACKGROUND: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers.

    PURPOSE OF THE STUDY: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability.

    MATERIALS AND METHODS: NP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation.

    RESULTS: The hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3-74.31 ± 17.7 μm with Span index values of 0.491-0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent "n" value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (-3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed.

    CONCLUSION: The current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.

  13. Si LY, Ramalingam A, Ali SS, Aminuddin A, Ng PY, Latip J, et al.
    EXCLI J, 2019;18:876-892.
    PMID: 31645847 DOI: 10.17179/excli2019-1792
    Roselle (Hibiscus sabdariffa Linn) has been traditionally used as folk medicine for hypertension and maintaining cardiovascular health, with therapeutic potential in protecting against numerous cardiovascular diseases. However, it remains unclear whether roselle can be used for management of cardiac hypertrophy seen after myocardial infarction (MI). This study therefore investigated the effects of aqueous roselle extract on cardiac hypertrophy arising from myocardial infarction both in vivo and in vitro. For in vivo study, male Sprague-Dawley rats were divided into control or MI groups (receiving 85 mg/kg isoproterenol s.c. for 2 days) and were given roselle extract (100 mg/kg, p.o daily) for 28 days. Cardiac structure and functional changes were evaluated at study end-point using histology, Langendorff analysis and gene expression analysis. In vitro effects of roselle were also assessed on ANG II-induced cardiomyocytes hypertrophy using H9c2 cells, simulating cardiac hypertrophy evident after MI. Roselle significantly ameliorated MI-induced cardiac systolic and diastolic dysfunction, as seen across improvement in left ventricular developed pressure (LVDP) and its derivative (LVdP/dtmax) and isovolumic relaxation (Tau). Oxidative stress evident across elevated pro-oxidant markers (NOX2 subunit of NADPH oxidase and 8-isoprostane) as well as reduced antioxidant markers (superoxide dismutase and glutathione) were also significantly attenuated by roselle. Furthermore, roselle treatment markedly reduced markers of cardiac remodeling (cardiac hypertrophy and fibrosis) compared to the untreated MI rats. On in vitro analysis, roselle significantly attenuated ANG II-induced cardiomyoycte hypertrophy in dose-dependent manner. This study demonstrated that roselle attenuates cardiac hypertrophy and dysfunction seen after MI both in vivo and in vitro, and these effects are likely mediated by phenolic compounds found in roselle extract.
  14. Madadi M, Liu D, Qin Y, Zhang Y, Karimi K, Tabatabaei M, et al.
    Bioresour Technol, 2023 Sep;384:129370.
    PMID: 37343805 DOI: 10.1016/j.biortech.2023.129370
    This work aimed to study an integrated pretreatment technology employing p-toluenesulfonic acid (TsOH)-catalyzed liquid hot water (LHW) and short-time ball milling for the complete conversion of poplar biomass to xylooligosaccharides (XOS), glucose, and native-like lignin. The optimized TsOH-catalyzed LHW pretreatment solubilized 98.5% of hemicellulose at 160 °C for 40 min, releasing 49.8% XOS. Moreover, subsequent ball milling (20 min) maximized the enzymatic hydrolysis of cellulose from 65.8% to 96.5%, owing to the reduced particle sizes and cellulose crystallinity index. The combined pretreatment reduced the crystallinity by 70.9% while enlarging the average pore size and pore volume of the substrate by 29.5% and 52.4%, respectively. The residual lignin after enzymatic hydrolysis was rich in β-O-4 linkages (55.7/100 Ar) with less condensed structures. This lignin exhibited excellent antioxidant activity (RSI of 66.22) and ultraviolet absorbance. Thus, this research suggested a sustainable waste-free biorefinery for the holistic valorization of biomass through two-step biomass fractionation.
  15. Ali I, Wei DQ, Khan A, Feng Y, Waseem M, Hussain Z, et al.
    PMID: 38287712 DOI: 10.1002/bab.2548
    Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.
  16. Ali SS, Asman A, Shao J, Firmansyah AP, Susilo AW, Rosmana A, et al.
    PMID: 31583107 DOI: 10.1186/s40694-019-0077-6
    Background: Ceratobasidium theobromae, a member of the Ceratobasidiaceae family, is the causal agent of vascular-streak dieback (VSD) of cacao, a major threat to the chocolate industry in the South-East Asia. The fastidious pathogen is very hard to isolate and maintain in pure culture, which is a major bottleneck in the study of its genetic diversity and genome.

    Result: This study describes for the first time, a 33.90 Mbp de novo assembled genome of a putative C. theobromae isolate from cacao. Ab initio gene prediction identified 9264 protein-coding genes, of which 800 are unique to C. theobromae when compared to Rhizoctonia spp., a closely related group. Transcriptome analysis using RNA isolated from 4 independent VSD symptomatic cacao stems identified 3550 transcriptionally active genes when compared to the assembled C. theobromae genome while transcripts for only 4 C. theobromae genes were detected in 2 asymptomatic stems. De novo assembly of the non-cacao associated reads from the VSD symptomatic stems uniformly produced genes with high identity to predicted genes in the C. theobromae genome as compared to Rhizoctonia spp. or genes found in Genbank. Further analysis of the predicted C. theobromae transcriptome was carried out identifying CAZy gene classes, KEGG-pathway associated genes, and 138 putative effector proteins.

    Conclusion: These findings put forth, for the first time, a predicted genome for the fastidious basidiomycete C. theobromae causing VSD on cacao providing a model for testing and comparison in the future. The C. theobromae genome predicts a pathogenesis model involving secreted effector proteins to suppress plant defense mechanisms and plant cell wall degrading enzymes.

  17. Karim SS, Murtaza Z, Farrukh S, Umer MA, Ali SS, Younas M, et al.
    Environ Res, 2022 Apr 01;205:112402.
    PMID: 34838569 DOI: 10.1016/j.envres.2021.112402
    The emerging growth of the electronic devices applications has arisen the serious problems of electromagnetic (EM) wave pollution which resulting in equipment malfunction. Therefore, polymer-based composites have been considered good candidates for better EMI shielding due to their significant characteristics including, higher flexibility, ultrathin, lightweight, superior conductivity, easy fabrication processing, environmentally friendly, corrosion resistive, better adhesion with physical, chemical and thermal stability. This review article focused on the concept of the EMI shielding mechanism and challenges with the fabrication of polymer-based composites. Subsequently, recent advancements in the polymer composites applications have been critically reviewed. In addition, the impact of polymers and polymer nanocomposites with different fillers such as organic, inorganic, 2D, 3D, mixture and hybrid nano-fillers on EMI shielding effectiveness has been explored. Lastly, future research directions have been proposed to overcome the limitations of current technologies for further advancement in EMI shielding materials for industrial applications. Based on reported literature, it has been found that the low thickness based lightweight polymer is considered as a best material for excellent material for next-generation electronic devices. Optimization of polymer composites during the fabrication is required for better EMI shielding. New nano-fillers such as functionalization and composite polymers are best to enhance the EMI shielding and conductive properties.
  18. Khan A, Hussain S, Ahmad S, Suleman M, Bukhari I, Khan T, et al.
    Comput Biol Med, 2022 02;141:105163.
    PMID: 34979405 DOI: 10.1016/j.compbiomed.2021.105163
    The spike protein of SARS-CoV-2 and the host ACE2 receptor plays a vital role in the entry to the cell. Among which the hotspot residue 501 is continuously subjected to positive selection pressure and induces unusual virulence. Keeping in view the importance of the hot spot residue 501, we predicted the potentially emerging structural variants of 501 residue. We analyzed the binding pattern of wild type and mutants (Spike RBD) to the ACE2 receptor by deciphering variations in the amino acids' interaction networks by graph kernels along with evolutionary, network metrics, and energetic information. Our analysis revealed that N501I, N501T, and N501V increase the binding affinity and alter the intra and inter-residue bonding networks. The N501T has shown strong positive selection and fitness in other animals. Docking results and repeated simulations (three times) confirmed the structural stability and tighter binding of these three variants, correlated with the previous results following the global stability trend. Consequently, we reported three variants N501I, N501T, and N501V could worsen the situation further if they emerged. The relations between the viral fitness and binding affinity is a complicated game thus the emergence of high affinity mutations in the SARS-CoV-2 RBD brings up the question of whether or not positive selection favours these mutations or not?
  19. Khan A, Randhawa AW, Balouch AR, Mukhtar N, Sayaf AM, Suleman M, et al.
    RSC Adv, 2022 Mar 01;12(12):7318-7327.
    PMID: 35424688 DOI: 10.1039/d2ra00277a
    A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links