Displaying publications 61 - 80 of 97 in total

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  1. Fong MY, Rashdi SA, Yusof R, Lau YL
    PLoS One, 2016;11(5):e0155627.
    PMID: 27195821 DOI: 10.1371/journal.pone.0155627
    BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPαRII) and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkγRII) is not involved in the invasion of P. knowlesi into humans. PkγRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPαRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPαRII was observed to be undergoing purifying (negative) selection. The present study aimed to determine whether similar phenomena occur in PkγRII.

    METHODS: Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3).

    RESULTS: A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd) and nucleotide diversity (π) with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative) selection, geographical clustering of haplotypes, and high inter-population genetic differentiation (FST index). The main differences between PkγRII and PkDBPαRII include length polymorphism and no departure from neutrality (as measured by Tajima's D statistics) in the PkγRII.

    CONCLUSION: Despite the biological difference between PkγRII and PkDBPαRII, both generally have similar genetic diversity level, natural selection, geographical haplotype clustering and inter-population genetic differentiation index.

  2. Rothan HA, Amini E, Faraj FL, Golpich M, Teoh TC, Gholami K, et al.
    Sci Rep, 2017 03 30;7:45540.
    PMID: 28358047 DOI: 10.1038/srep45540
    N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.
  3. Mahmod SA, Snigh S, Djordjevic I, Mei Yee Y, Yusof R, Ramasamy TS, et al.
    Tissue Eng Regen Med, 2017 Apr;14(2):103-112.
    PMID: 30603467 DOI: 10.1007/s13770-016-0004-3
    Clinical investigations have shown a significant relationship between osteoarthritis (OA) and estrogens levels in menopausal women. Therefore, treatment with exogenous estrogens has been shown to decrease the risk of OA. However, the effect estrogen has not been clearly demonstrated in the chondrocytes using phytoestrogens, which lack the specific side-effects of estrogens, may provide an alternative therapy. This study was designed to examine the possible effects of phytoestrogen (daidzein) on human chondrocyte phenotype and extracellular matrix formation. Phytoestrogens which lack the specific side-effects of estrogens may provide beneficial effect without causing hormone based side effect. Human chondrocytes cells were cultured in 2D (flask) and 3D (PCL-CA scaffold) systems. Daidzein cytotoxic effect was determined by MTT assay. Chondrocyte cellular content of glycosaminoglycans (GAGs), total collagen and chondrogenic gene expression were determined in both culture systems after treatment with daidzein. Daidzein showed time-dependent and dose-independent effects on chondrocyte bioactivity. The compound at low doses showed significant (p  0.05). The expression levels of Fibronectin, Laminin and Integrin β1 were significantly increased especially in 3D culture system. This study was illustrated the potential positive effects of daidzein on maintenance of human chondrocyte phenotype and extracellular matrix formation suggesting an attractive and viable alternative therapy for OA.
  4. Rothan HA, Mahmod SA, Djordjevic I, Golpich M, Yusof R, Snigh S
    Tissue Eng Regen Med, 2017 Apr;14(2):93-101.
    PMID: 30603466 DOI: 10.1007/s13770-017-0023-8
    In this paper we report the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes within elastomeric polycaprolactone triol-citrate (PCLT-CA) porous scaffold. Human-derived chondrocyte cellular content of glycosaminoglycans (GAGs) and total collagen were determined after seeding into PCLT-CA scaffold enriched with PRPr cells. Immunostaining and real time PCR was applied to evaluate the expression levels of chondrogenic and extracellular gene markers. Seeding of chondrocytes into PCLT-CA scaffold enriched with PRPr showed significant increase in total collagen and GAGs production compared with chondrocytes grown within control scaffold without PRPr cells. The mRNA levels of collagen II and SOX9 increased significantly while the upregulation in Cartilage Oligomeric Matrix Protein (COMP) expression was statistically insignificant. We also report the reduction of the expression levels of collagen I and III in chondrocytes as a consequence of proximity to PRPr cells within the scaffold. Interestingly, the pre-loading of PRPr caused an increase of expression levels of following extracellular matrix (ECM) proteins: fibronectin, laminin and integrin β over the period of 3 days. Overall, our results introduce the PCLT-CA elastomeric scaffold as a new system for cartilage tissue engineering. The method of PRPr cells loading prior to chondrocyte culture could be considered as a potential environment for cartilage tissue engineering as the differentiation and ECM formation is enhanced significantly.
  5. Amir-Hassan A, Lee VS, Baharuddin A, Othman S, Xu Y, Huang M, et al.
    J Mol Graph Model, 2017 06;74:273-287.
    PMID: 28458006 DOI: 10.1016/j.jmgm.2017.03.010
    Effective novel peptide inhibitors which targeted the domain III of the dengue envelope (E) protein by blocking dengue virus (DENV) entry into target cells, were identified. The binding affinities of these peptides towards E-protein were evaluated by using a combination of docking and explicit solvent molecular dynamics (MD) simulation methods. The interactions of these complexes were further investigated by using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area (MMGBSA) methods. Free energy calculations of the peptides interacting with the E-protein demonstrated that van der Waals (vdW) and electrostatic interactions were the main driving forces stabilizing the complexes. Interestingly, calculated binding free energies showed good agreement with the experimental dissociation constant (Kd) values. Our results also demonstrated that specific residues might play a crucial role in the effective binding interactions. Thus, this study has demonstrated that a combination of docking and molecular dynamics simulations can accelerate the identification process of peptides as potential inhibitors of dengue virus entry into host cells.
  6. Koh KC, Islam M, Chan WK, Lee WY, Ho YW, Alsagoff SAH, et al.
    Med J Malaysia, 2017 08;72(4):209-214.
    PMID: 28889131
    INTRODUCTION: In Malaysia, the prevalence of missed opportunities for HIV-testing is unknown. Missed opportunities have been linked to late diagnosis of HIV and poorer outcome for patients. We describe missed opportunities for earlier HIV-testing in newly-HIV-diagnosed patients.

    METHODS: Cross sectional study. Adult patients diagnosed with HIV infection and had at least one medical encounter in a primary healthcare setting during three years prior to diagnosis were included. We collected data on sociodemographic characteristics, patient characteristics at diagnosis, HIV-related conditions and whether they were subjected to risk assessment and offered HIV testing during the three years prior to HIV diagnosis.

    RESULTS: 65 newly HIV-diagnosed patients (male: 92.3%; Malays: 52.4%; single: 66.7%; heterosexual: 41%; homosexual 24.6%; CD4 <350 at diagnosis: 63%). 93.8% were unaware of their HIV status at diagnosis. Up to 56.9% had presented with HIV-related conditions at a primary healthcare facility during the three years prior to diagnosis. Slightly more than half were had risk assessment done and only 33.8% were offered HIV-testing.

    CONCLUSIONS: Missed opportunities for HIV-testing was unacceptably high with insufficient risk assessment and offering of HIV-testing. Risk assessment must be promoted and primary care physicians must be trained to recognize HIV-related conditions that will prompt them to offer HIVtesting.

  7. Lim KK, Chan YY, Teh CH, Ismail H, Yusof R, Muhi J, et al.
    Asia Pac J Clin Nutr, 2017 8 15;26(5):861-866.
    PMID: 28802296 DOI: 10.6133/apjcn.092016.06
    BACKGROUND AND OBJECTIVES: In 2000, legislation on mandatory universal salt iodisation was enacted in Sabah, Malaysia, to reduce the incidence of iodine deficiency disorders among its population. To evaluate the iodine levels among pregnant women from selected rural divisions in Sabah 13 years after the enactment of the universal salt iodisation programme.

    METHODS AND STUDY DESIGN: This cross-sectional study was conducted from 1 May to 30 June, 2013, in three rural divisions of Sabah (the Interior, the West Coast, and Kudat). Data regarding domestic iodised salt use and iodine-containing supplement consumption were obtained from respondents through face-to-face interviews; goitre enlargement was examined through palpation and graded according to the World Health Organization classification. Spot urine samples were also obtained to assess urinary iodine levels by using an in-house modified micromethod.

    RESULTS: In total, 534 pregnant women participated. The prevalence of goitre was 1.0% (n=5), noted only in the West Coast and Kudat divisions. Although all pregnant women consumed iodised salt, overall median urinary iodine concentration was only 106 μg/L, indicating insufficient iodine intake, with nearly two-thirds of the women (60%) having a median urinary iodine concentrations of <150 μg/L.

    CONCLUSIONS: Pregnant women from the rural divisions in Sabah still exhibit iodine deficiency disorder despite the mandatory universal salt iodisation programme. Iodine supplementation programmes targeting pregnant women are warranted.

  8. Gan CS, Lim PJ, Razif MF, Yusof R, Othman S
    Rev Soc Bras Med Trop, 2017 Jan-Feb;50(1):99-103.
    PMID: 28327809 DOI: 10.1590/0037-8682-0207-2016
    INTRODUCTION:: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2).

    METHODS:: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified.

    RESULTS:: Results demonstrated sequestration of immunoproteasome subunits LMP2 and LMP7 in DV2-infected cells.

    CONCLUSIONS:: This study provides insights into the mechanisms underlying immune evasion by DV.
  9. Yasin ZAM, Ibrahim F, Rashid NN, Razif MFM, Yusof R
    Curr Pharm Biotechnol, 2017;18(11):864-876.
    PMID: 29256348 DOI: 10.2174/1389201019666171219105920
    BACKGROUND: Skin is the largest and most visible organ of the body. Many of its functions include temperature regulation, immunity from microorganisms, maintaining electrolyte balance, and protection from physical injuries, chemical agents and ultraviolet (UV) radiation. Aging occurs in every layer of the skin, primarily due to the degradation of its components. Induction of degradative enzymes and the abundant production of reactive oxygen species lead to skin aging. Understanding the complexity of skin structure and factors contributing to the skin aging will help us impede the aging process. Applications of anti-aging products are a common method to prevent or repair damages that lead to aging.

    CONCLUSION: This review will provide information on the causes and indicators of skin aging as well as examine studies that have used plants to produce anti-aging products.

  10. Lim SK, Othman R, Yusof R, Heh CH
    Curr Comput Aided Drug Des, 2017;13(2):160-169.
    PMID: 27903217 DOI: 10.2174/1573409912666161130122622
    BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximately 3% of the global populations. Despite the current several direct antiviral agents in the treatment of Hepatitis C, the standard treatment for HCV infection is accompanied by several drawbacks, such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants.

    OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach.

    METHODS: In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of AutoDock Vina and in situ minimization were to account for the non-deterministic nature of AutoDock Vina search algorithm and binding site flexibility, respectively. ADME/T and interaction analyses were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5.

    RESULTS: This study involved the development of an improved flow for virtual screening via implemention of multiple-seeding screening approach and in situ minimization. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. Ten benzopyran-like compounds with satisfactory physicochemical properties were discovered to be potential inhibitors of HCV helicase. ZINC38649350 was identified as the most potential inhibitor.

    CONCLUSION: Ten potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serve as an alternative approach of in silico rational drug discovery.

  11. Gan CS, Lim SK, Chee CF, Yusof R, Heh CH
    Chem Biol Drug Des, 2018 02;91(2):448-455.
    PMID: 28834304 DOI: 10.1111/cbdd.13091
    Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
  12. Shafie MH, Samsudin D, Yusof R, Gan CY
    Int J Biol Macromol, 2018 Oct 15;118(Pt A):1183-1192.
    PMID: 29944943 DOI: 10.1016/j.ijbiomac.2018.06.103
    Momordica charantia bioactive polysaccharide (MCBP) was used as an alternative source for the production of bio-based plastics (BPs) with choline chloride/glycerol-based deep eutectic solvent (DES) as a plasticizer. In this study, MCBP was initially extracted using 0.1 M citric acid at temperature 80 °C for 2 h, precipitated using ethanol, and then lyophilized. Subsequently, seven BPs were prepared: MCBP without plasticizer (MCBP), with 1% (w/w) of glycerol (MCBP-G), or with 1% (w/w) of DES at different choline chloride/glycerol molar ratios (i.e. 1.5:1, 1:1, 1:1.5, 1:2, and 1:3). The properties of these BPs were then investigated. Results showed that the tensile strains, stresses and moduli were in the range of 1.3-13.3%, 4.8-19.1 MPa and 132-2487 MPa, respectively. The melting temperatures were found in the range of 92.6-111.4 °C whereas the moisture absorptions and water vapour transmission rates (WVTR) of BPs were 1.4-6.5% and 3.6-5.4 mg/m2·s, respectively. The results also showed that these BPs exhibited bioactivities, such as microbial inhibitory activity (19.5-32.3 mm), free radical scavenging activity (10.3-18.3%) and ferric reducing antioxidant power (FRAP, 16.1-20.0 mM). In addition, it was observed that using DES as a plasticizer had improved the properties of BP, such as tensile strain (354.7-937.5%), melting temperature (4.6-20.3%), radical scavenging activity (0.6-88.6%), FRAP (0.9-18.7%) and antimicrobial activity (12.3-33.6%) compared to MCBP, due to the fact DES has caused different degrees of plasticization via hydrogen bonds and ionic bonds with the polymer chains, and induced a lower pH condition. Therefore, it was suggested that these BPs with DES could contribute to food preservation properties.
  13. Abduraman MA, Hariono M, Yusof R, Rahman NA, Wahab HA, Tan ML
    Heliyon, 2018 Dec;4(12):e01023.
    PMID: 30560214 DOI: 10.1016/j.heliyon.2018.e01023
    Background: Dengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities.

    Methods: The assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format.

    Results: The optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable z' factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities.

    Conclusion: The AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.

  14. Tan WL, Lee YK, Ho YF, Yusof R, Abdul Rahman N, Karsani SA
    PeerJ, 2018;5:e3939.
    PMID: 29404200 DOI: 10.7717/peerj.3939
    Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda) that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.
  15. Shafie MH, Yusof R, Gan CY
    Carbohydr Polym, 2019 Jul 15;216:303-311.
    PMID: 31047070 DOI: 10.1016/j.carbpol.2019.04.007
    The Box-Behnken design was applied to optimize the extraction of pectin from Averrhoa bilimbi (ABP) using deep eutectic solvents (DES). The four variables of extraction were percentage of DES (X1), extraction time (X2), temperature (X3), and molar ratio of DES components (X4). The quadratic regression equation was established as a predicted model with R2 value of 0.9375. The optimal condition was X1 = 3.74% (w/v), X2 = 2.5 h, X3 = 80 °C, and X4 = 1:1. No significant difference between the predicted (14.70%) and experimental (14.44%) maximum yield of sample was noted. Characterization of physico-chemical properties characterization of ABP was performed. The main components of ABP were galacturonic acids, arabinoses, and xyloses. ABP also showed good functional properties such as water holding capacity (3.70 g/g), oil holding capacity (2.40 g/g), and foaming capacity (133.33%). The results also showed that ABP exhibited free radical scavenging activity (41.46%) and ferric reducing antioxidant power (1.15 mM).
  16. Rothan HA, Abdulrahman AY, Khazali AS, Nor Rashid N, Chong TT, Yusof R
    J. Pept. Sci., 2019 Aug;25(8):e3196.
    PMID: 31290226 DOI: 10.1002/psc.3196
    Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted to humans by their common vector, Aedes mosquitoes. DENV infection represents one of the most widely spread mosquito-borne diseases whereas ZIKV infection occasionally re-emerged in the past causing outbreaks. Although there have been considerable advances in understanding the pathophysiology of these viruses, no effective vaccines or antiviral drugs are currently available. In this study, we evaluated the antiviral activity of carnosine, an endogenous dipeptide (β-alanyl-l-histidine), against DENV serotype 2 (DENV2) and ZIKV infection in human liver cells (Huh7). Computational studies were performed to predict the potential interactions between carnosine and viral proteins. Biochemical and cell-based assays were performed to validate the computational results. Mode-of-inhibition, plaque reduction, and immunostaining assays were performed to determine the antiviral activity of carnosine. Exogenous carnosine showed minimal cytotoxicity in Huh7 cells and rescued the viability of infected cells with EC50 values of 52.3 and 59.5 μM for DENV2 and ZIKV infection, respectively. Based on the mode-of-inhibition assays, carnosine inhibited DENV2 mainly by inhibiting viral genome replication and interfering with virus entry. Carnosine antiviral activity was verified with immunostaining assay where carnosine treatment diminished viral fluorescence signal. In conclusion, carnosine exhibited significant inhibitory effects against DENV2 and ZIKV replication in human liver cells and could be utilized as a lead peptide for the development of effective and safe antiviral agents against DENV and ZIKV.
  17. Shukri M, Min RM, Abdullah SS, Yusof RAM, Husain Z
    Med J Malaysia, 2019 Oct;74(5):377-384.
    PMID: 31649212
    INTRODUCTION: In recognition of the role of motivation in drug use treatment, patient motivational screening instruments are needed for strategic planning and treatment. The aims of this study were to evaluate the reliability and validity of the Malay version of the Treatment Motivation Scale, and to compare the motivational levels of patients receiving substance abuse treatment with different modalities (inpatient vs. outpatient). The motivational scale consists of three scales: problem recognition, desire for help and treatment readiness.

    METHOD: A convenience sample of 102 patients was recruited from four Cure and Care Service Centres in Malaysia.

    RESULTS: Principal component analysis with varimax rotation supported two-factor solutions for each subscale: problem recognition, desire for help and treatment readiness, which accounted for 63.5%, 62.7% and 49.1% of the variances, respectively. The Cronbach's alpha coefficients were acceptable for the overall measures (24 items: ∝ = 0.89), the problem recognition scale (10 items; ∝ = 0.89), desire for help (6 items; ∝ = 0.64) and treatment readiness scale (8 items; ∝ = 0.60). The results also indicated significant motivational differences for different modalities, with inpatients having significantly higher motivational scores in each scale compared to outpatients.

    CONCLUSION: The present study pointed towards the favourable psychometric properties of a motivation for treatment scale, which can be a useful instrument for clinical applications of drug use changes and treatment.

  18. Rothan HA, Zhong Y, Sanborn MA, Teoh TC, Ruan J, Yusof R, et al.
    Antiviral Res, 2019 11;171:104590.
    PMID: 31421166 DOI: 10.1016/j.antiviral.2019.104590
    Two major flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), cause severe health and economic burdens worldwide. Recently, genome-wide screenings have uncovered the importance of regulators of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway for flavivirus replication in host cells. Here we report the identification of the compound Bardoxolone methyl (CDDO-me) as a potent inhibitor of the Hrd1 ubiquitin ligase-mediated ERAD, which possesses a broad-spectrum activity against both DENV and ZIKV. Cellular thermal shift assay (CETSA) suggested that CDDO-me binds to grp94, a key component of the Hrd1 pathway, at a low nanomolar concentration, whereas interaction was not detected with its paralog Hsp90. CDDO-me and the grp94 inhibitor PU-WS13 substantially suppressed DENV2 replication and the cytopathic effects caused by DENV and ZIKV infection. The antiviral activities of both compounds were demonstrated for all four DENV serotypes and four ZIKV strains in multiple human cell lines. This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
  19. Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, et al.
    PLoS One, 2019;14(1):e0210869.
    PMID: 30677071 DOI: 10.1371/journal.pone.0210869
    Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.
  20. Arfa R, Yusof R, Shabanzadeh P
    PeerJ Comput Sci, 2019;5:e206.
    PMID: 33816859 DOI: 10.7717/peerj-cs.206
    Trajectory clustering and path modelling are two core tasks in intelligent transport systems with a wide range of applications, from modeling drivers' behavior to traffic monitoring of road intersections. Traditional trajectory analysis considers them as separate tasks, where the system first clusters the trajectories into a known number of clusters and then the path taken in each cluster is modelled. However, such a hierarchy does not allow the knowledge of the path model to be used to improve the performance of trajectory clustering. Based on the distance dependent Chinese restaurant process (DDCRP), a trajectory analysis system that simultaneously performs trajectory clustering and path modelling was proposed. Unlike most traditional approaches where the number of clusters should be known, the proposed method decides the number of clusters automatically. The proposed algorithm was tested on two publicly available trajectory datasets, and the experimental results recorded better performance and considerable improvement in both datasets for the task of trajectory clustering compared to traditional approaches. The study proved that the proposed method is an appropriate candidate to be used for trajectory clustering and path modelling.
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