Displaying publications 81 - 100 of 125 in total

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  1. Fulltext Effect of abiotic stress on carotenoids accumulation in pumpkin plants under light and dark conditions
    Norshazila, S., Othman, R., Jaswir, I., Yumi Zuhanis, H.H.
    International Food Research Journal, 2017;24(101):0-0.
    MyJurnal
    In nature, environmental factors highly influence the carotenoid composition in pumpkin plants and these factors were difficult to control; thus, carotenoid content is varied quantitatively and qualitatively. However, certain parameters can be controlled and this can be conducted in the laboratory through biogenesis manipulation. This approach uses environmental stress as a tool to alter the carotenoid pathway in the plants. The main objective of this study was to observe the inhibiting and enhancing effect of abiotic stress on individual carotenoid accumulation in pumpkin plants under light and dark conditions. The abiotic stresses used were plant elicitors which consisted of Ultra Violet light exposure, Polyethylene Glycol 4000, Salicylic Acid, and half strength nutrients using Murashige and Skoog Salt. After two weeks of treatments, the pumpkin leaves and stems were harvested, freeze dried and extracted to determine the carotenoids compound using High-Performance Liquid Chromatography (HPLC). Results showed that there was a significant difference (p
  2. Fulltext Determination of permissible alcohol and vinegar in Shariah and scientific perspectives
    Jamaludin, M.A., Hashim, D.M., Rahman, R.A., Ramli, M.A., Majid, M.Z.A., Othman, R., et al.
    International Food Research Journal, 2016;23(6):2737-2743.
    MyJurnal
    The halal food production industry is gaining greater attention among Muslim and non-Muslim
    majority countries, particularly due to the increase of global market demand. One of the critical
    areas in issuing halal certified food is the determination of allowable alcohol content in food
    and drinks. The level of alcohol content has not standardized in several standards and fatwa of
    Islamic scholars. In Islam, the alcohol in several fruit products is produced through fermentation
    process such as takhammur (wine making) and takhallul (vinegar making). The fermentation
    process gives an impact to the status of the food products either permissible or prohibited.
    Therefore, the purpose of this paper is to discuss on the determination of permissible alcohol
    and vinegar by fermentation process content in selected food products from Shariah and science
    perspectives. In doing so, the views of authentic of Islamic Law in this issue are supported by
    lab work approached. As a result, in the first phase there are three types of by products from
    takhammur, while two types of takhallul. All the products can be determine of the alcohol
    content and give an implication of the status either permissible (halal) or prohibited (haram).
    Hence, in juice considered as halal due to lower of alcohol content. While cider or alcoholic
    beverage is haram due to above alcohol level permitted which is above of the 1%. Besides,
    cider vinegar or vinegar is halal by the interpretation of hadith of permissible conversion from
    alcoholic to vinegar itself.
  3. Analysis of secondary structure predictions of dengue virus type 2 NS2B/NS3 against crystal structure to evaluate the predictive power of the in silico methods
    Othman R, Wahab HA, Yusof R, Rahman NA
    In Silico Biol. (Gedrukt), 2007;7(2):215-24.
    PMID: 17688447
    Multiple sequence alignment was performed against eight proteases from the Flaviviridae family using ClustalW to illustrate conserved domains. Two sets of prediction approaches were applied and the results compared. Firstly, secondary structure prediction was performed using available structure prediction servers. The second approach made use of the information on the secondary structures extracted from structure prediction servers, threading techniques and DSSP database of some of the templates used in the threading techniques. Consensus on the one-dimensional secondary structure of Den2 protease was obtained from each approach and evaluated against data from the recently crystallised Den2 NS2B/NS3 obtained from the Protein Data Bank (PDB). Results indicated the second approach to show higher accuracy compared to the use of prediction servers only. Thus, it is plausible that this approach is applicable to the initial stage of structural studies of proteins with low amino acid sequence homology against other available proteins in the PDB.
  4. Variable clinical phenotypes in a family with homozygous c.1159G>A mutation in the thyroid peroxidase gene
    Lee CC, Harun F, Jalaludin MY, Heh CH, Othman R, Kang IN, et al.
    Horm Res Paediatr, 2014;81(5):356-60.
    PMID: 24717978 DOI: 10.1159/000359922
    Defects in the thyroid peroxidase (TPO) gene have been associated with goitrous congenital hypothyroidism (CH).
  5. Fulltext Isolation and characterization of novel microsatellite markers in commercial selected golden Malaysian arowana fish, Scleropages formosus (Osteoglossidae)
    Manoharan B, Sulaimen Z, Omar F, Othman RY, Mohamed SZ, Bhassu S
    Genet. Mol. Res., 2011;10(2):712-6.
    PMID: 21523650 DOI: 10.4238/vol10-2gmr944
    Malaysian arowana (dragonfish; Scleropages formosus) is an ancient osteoglossid fish from southeast Asia. Due to the high demand of the ornamental fish trade and because of habitat loss, the species is close to extinction. We isolated and characterized 10 polymorphic microsatellites of this species, using 5'-anchored PCR. The number of alleles at the 10 microsatellite loci ranged from 2 to 28, with a mean of 7.8/locus. The observed heterozygosity ranged from 0.03 to 0.93 (mean: 0.39), whereas the expected heterozygosity ranged from 0.03 to 0.94 (mean: 0.46). Seven microsatellites deviated from Hardy-Weinberg equilibrium, and three conformed to Hardy-Weinberg equilibrium and were in linkage equilibrium. These 10 novel microsatellites should facilitate studies of genetic diversity and population structure of arowana to help plan actions for the conservation of the indigenous Malaysian arowana.
  6. Fulltext Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia
    Lee TY, Lai MI, Ismail P, Ramachandran V, Tan JA, Teh LK, et al.
    Genet. Mol. Res., 2016 Apr 07;15(2).
    PMID: 27173219 DOI: 10.4238/gmr.15027400
    Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.
  7. Fulltext The moderating effect of perceived organizational support: The impact of psychological capital and bidirectional work-family nexuses on psychological wellbeing in tourism
    Bai N, Yan Z, Othman R
    Front Psychol, 2023;14:1064632.
    PMID: 36910770 DOI: 10.3389/fpsyg.2023.1064632
    The novel coronavirus (COVID-19) has inflicted unprecedented damage on the tourism industry. However, the psychological health fallout of COVID-19 on tour guides has not received empirical attention yet. Therefore, the present study aims to examine how psychological capital (PsyCap) improve tour guides' psychological wellbeing (PWB), the mediating effects of work-family conflict (WFC), family-work conflict (FWC), work-family facilitation (WFF) and family-work facilitation (FWF), and the moderating effect of perceived organizational support (POS). For this quantitative research, the data were collected from 276 tour guides in China. The results indicate that PsyCap significantly mitigates two directions of work-family conflict and intensifies two directions of work-family facilitation in order to promote tour guides' PWB. Furthermore, POS moderates the direct effects of two directions of conflict and facilitation on PWB and also moderates the indirect effects of PsyCap on the aforesaid outcome via two directions of conflict and facilitation. Theoretical and practical implications, limitations and future research directions are provided.
  8. The effect of methyltestosterone (MT) on sex differentiation and growth in juvenile yellow perch (Perca flavescens)
    Othman R, Ron XJ, Yao H, O'Bryant P, Rapp D, Pei JC, et al.
    Fish Physiol Biochem, 2022 Feb;48(1):161-171.
    PMID: 35039993 DOI: 10.1007/s10695-021-01038-0
    A study was conducted to evaluate the gonad differentiation of juvenile yellow perch (YP, Perca flavencens) and determine the latest labile period related to hormone treatment. Juvenile fish were subjected to two dietary concentrations of methyltestosterone (MT; 20 and 50 mg/kg feed) for 60 days in three (3) age groups of 38-, 46-, and 67-days post-hatching (dph), where control group were fed with standard commercial feed. Following a 10-month on-growing period, sex phenotypes were determined by gross and histological gonad morphology. Results showed the juvenile YP responded to the exogenous hormone when it was applied at 38 dph for both 20 and 50 mg/kg feed resulting in 100% males. At 46 dph, only 50 mg/kg feed resulted in 100% males. Both MT-treated at 38 and 46 dph significantly differed (P 
  9. Fulltext Engineering the lactococcal mevalonate pathway for increased sesquiterpene production
    Song AA, Abdullah JO, Abdullah MP, Shafee N, Othman R, Noor NM, et al.
    FEMS Microbiol Lett, 2014 Jun;355(2):177-84.
    PMID: 24828482 DOI: 10.1111/1574-6968.12469
    Isoprenoids are a large, diverse group of secondary metabolites which has recently raised a renewed research interest due to genetic engineering advances, allowing specific isoprenoids to be produced and characterized in heterologous hosts. Many researches on metabolic engineering of heterologous hosts for increased isoprenoid production are focussed on Escherichia coli and yeasts. E. coli, as most prokaryotes, use the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway for isoprenoid production. Yeasts on the other hand, use the mevalonate pathway which is commonly found in eukaryotes. However, Lactococcus lactis is an attractive alternative host for heterologous isoprenoid production. Apart from being food-grade, this Gram-positive prokaryote uses the mevalonate pathway for isoprenoid production instead of the MEP pathway. Previous studies have shown that L. lactis is able to produce sesquiterpenes through heterologous expression of plant sesquiterpene synthases. In this work, we analysed the gene expression of the lactococcal mevalonate pathway through RT-qPCR to successfully engineer L. lactis as an efficient host for isoprenoid production. We then overexpressed the mvk gene singly or co-expressed with the mvaA gene as an attempt to increase β-sesquiphellandrene production in L. lactis. It was observed that co-expression of mvk with mvaA doubled the amount of β-sesquiphellandrene produced.
  10. Fulltext Boesenbergia rotunda: From Ethnomedicine to Drug Discovery
    Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.
    Evid Based Complement Alternat Med, 2012;2012:473637.
    PMID: 23243448 DOI: 10.1155/2012/473637
    Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
  11. In vitro and in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 and nitric oxide but not the suppression of NF-κB translocation
    Ibrahim Abdelwahab S, Syaed Koko W, Mohamed Elhassan Taha M, Mohan S, Achoui M, Ameen Abdulla M, et al.
    Eur J Pharmacol, 2012 Mar 5;678(1-3):61-70.
    PMID: 22227329 DOI: 10.1016/j.ejphar.2011.12.024
    Columbin, a diterpenoid furanolactone, was isolated purely for the first time from the plant species Tinspora bakis. The anti-inflammatory effects of columbin were studied in vitro, in silico and in vivo. The effect of columbin on nitric oxide was examined on lipopolysaccharide-interferon-gamma (LPS/IFN) induced RAW264.7 macrophages. In vitro and in silico cyclooxygenase-1 and cyclooxygenase-2 inhibitory activities of columbin using biochemical kit and molecular docking, respectively, were investigated. Mechanism of columbin in suppressing NF-kappaB-translocation was tested using Cellomics®NF-κB activation assay and ArrayScan Reader in LPS-stimulated RAW264.7 cells. Moreover, effects of columbin in vivo that were done on carrageenan-induced mice paw-oedema were tested. Lastly, the in vitro and in vivo toxicities of columbin were examined on human liver cells and mice, respectively. Treatment with columbin or N(ω)-nitro-l-arginine methyl ester (l-NAME) inhibited LPS/IFN-γ-induced NO production without affecting the viability of RAW264.7. Pre-treatment of stimulated cells with columbin did not inhibit the translocation of NF-κB to the nucleus in LPS-stimulated cells. COX-1 and COX-2 inhibitory activities of columbin were 63.7±6.4% and 18.8±1.5% inhibition at 100μM, respectively. Molecular docking study further helped in supporting the observed COX-2 selectivity. Whereby, the interaction of columbin with Tyr385 and Arg120 signifies its higher activity in COX-2, as Tyr385 was reported to be involved in the abstraction of hydrogen from C-13 of arachidonate, and Arg120 is critical for high affinity arachidonate binding. Additionally, columbin inhibited oedema formation in mice paw. Lastly, the compound was observed to be safe in vitro and in vivo. This study presents columbin as a potential anti-inflammatory drug.
  12. Key indicator tools for shallow slope failure assessment using soil chemical property signatures and soil colour variables
    Othman R, Hasni SI, Baharuddin ZM, Hashim KSH, Mahamod LH
    Environ Sci Pollut Res Int, 2017 Oct;24(29):22861-22872.
    PMID: 28721625 DOI: 10.1007/s11356-017-9715-9
    Slope failure has become a major concern in Malaysia due to the rapid development and urbanisation in the country. It poses severe threats to any highway construction industry, residential areas, natural resources and tourism activities. The extent of damages that resulted from this catastrophe can be lessened if a long-term early warning system to predict landslide prone areas is implemented. Thus, this study aims to characterise the relationship between Oxisols properties and soil colour variables to be manipulated as key indicators to forecast shallow slope failure. The concentration of each soil property in slope soil was evaluated from two different localities that consist of 120 soil samples from stable and unstable slopes located along the North-South Highway (PLUS) and East-West Highway (LPT). Analysis of variance established highly significant difference (P 
  13. Adsorption-desorption and leaching potential of glyphosate and aminomethylphosphonic acid in acidic Malaysian soil amended with cow dung and rice husk ash
    Garba J, Samsuri AW, Othman R, Ahmad Hamdani MS
    Environ Monit Assess, 2018 Oct 27;190(11):676.
    PMID: 30368595 DOI: 10.1007/s10661-018-7034-3
    This study investigates adsorption-desorption and the leaching potential of glyphosate and aminomethylphosphonic acid (AMPA) in control and amended-addition of cow dung or rice husk ash-acidic Malaysian soil with high oxide mineral content. The addition of cow dung or rice husk ash increased the adsorptive removal of AMPA. The isotherm data of glyphosate and AMPA best fitted the Freundlich model. The constant Kf for glyphosate was high in the control soil (544.873 mg g-1) followed by soil with cow dung (482.451 mg g-1) then soil with rice husk ash (418.539 mg g-1). However, for AMPA, soil with cow dung was high (166.636 mg g-1) followed by soil with rice husk ash (137.570 mg g-1) then the control soil (48.446 mg g-1). The 1/n values for both glyphosate and AMPA adsorptions were
  14. Bioluminescent method for the rapid screening of toxic heayy metals in environmental samples using Photobacterium leiognathi strain AK-MIE
    Kassim A, Halmi MIE, Gani SSA, Zaidan UH, Othman R, Mahmud K, et al.
    Ecotoxicol Environ Saf, 2020 Jun 15;196:110527.
    PMID: 32278138 DOI: 10.1016/j.ecoenv.2020.110527
    Assessment of eco-toxicant using bioluminescent bacterial assay is a widely used and globally accepted method. In this work, a new luminescent bacterium was isolated from squid (Loligo duvauceli) and identified as Photobacterium leiognathi strain AK-MIE using 16S rRNA, phylogeny analysis. The predicted optimum conditions by RSM were 2.76% (w/v) NaCl, 2.28% (w/v) peptone, 0.34% (w/v) yeast extract, and pH 6.83 with 541,211.80 RLU of luminescent production whereas the predicted optimum conditions by ANN were 2.21% (w/v) NaCl, 2.27% (w/v) peptone, 0.39% (w/v) yeast extract, and pH 6.94 which produced 541,986.20 RLU. The validation analysis of both RSM and ANN show 0.60% and 0.69% deviation from the predicted results indicating that both models provided good quality predictions with ANN showing a superior data fitting capability for non-linear regression analysis. Toxicity tests show strain AK-MIE was sensitive to mercury (concentration causing 50% inhibition or IC50 of 0.00978 mgL-1), followed by cadmium (IC50 of 0.5288 mgL-1), copper IC50 of (0.8117 mgL-1), silver (IC50 of 1.109 mgL-1), and lead (IC50 of 10.71 mgL-1) which are more sensitive than previously isolated luminescent bacteria, suggesting that strain AK-MIE has the potential to be used in toxicity assessment of heavy metals in the environment. Based on the field trial results, several sediment samples from industrial areas in Bangi, Selangor managed to inhibit the bioluminescence of strain AK-MIE. Validation method carried out using ICP-MS proved the presence of several toxic heavy metal elements.
  15. Fulltext Dataset for assessing the efficiency factors in Malaysian ports: Dry bulk terminal
    Rozar NM, Razik MA, Sidik MH, Kamarudin S, Ismail MR, Azid A, et al.
    Data Brief, 2020 Aug;31:105858.
    PMID: 32637478 DOI: 10.1016/j.dib.2020.105858
    This research paper provides for the identification of dry bulk terminal efficiencies on the basis of 10 key performance factors in Malaysian ports. Data were collected from 18 dry bulk ports in Malaysia in 2017 through an online questionnaire and distributed via e-mail. The dispersion of the respondents corresponds approximately to the structure of the Malaysian maritime terminal in dry bulk. The data provides port management perceptions towards 10 variables that have been surveyed. Each perception assessed the level of efficiency factors based on a percentage rate of 100%. Efficiency factors in dry bulk terminals have been identified with varying characteristics based on a descriptive analysis table. The dataset presented consists of a brief analysis of all 10 variables involved, including the minimum, maximum, mean, interquartile median and standard deviation. In addition to the descriptive analysis, the normality test and histogram were also performed. Data can be used to measure ports-efficiency factors in another research.
  16. Fulltext Transcriptome data of the carrageenophyte Eucheuma denticulatum
    Othman R, Abd Rasib AA, Ilias MA, Murthy S, Ismail N, Mohd Hanafi N
    Data Brief, 2019 Jun;24:103824.
    PMID: 30984808 DOI: 10.1016/j.dib.2019.103824
    Eucheuma denticulatum or commonly known as "Spinosum", is an economically important red alga that naturally grows on coral reefs with moderately strong currents in tropical and sub-tropical areas. This species is the primary source of iota-carrageenan which has high demands in the food, pharmaceutical and manufacturing industries, and as such it has been widely cultivated. The increasing global demand for carrageenan has led to extensive commercial cultivation of carrageenophytes mainly in the tropics. The carrageenophyte seaweeds including E. denticulatum are indigenous to Sabah, Malaysia. To enrich the information on the genes involved in carrageenan biosynthesis, RNA sequencing has been performed and transcriptomic dataset has been generated using Illumina HiSeq™ 2000 sequencer. The raw data and transcriptomic data have been deposited in NCBI database with the accession number PRJNA477734. These data will provide valuable resources for functional genomics annotation and investigation of mechanisms underlying the regulations of genes in this algal species.
  17. Fulltext Datasets of essential oils from naturally formed and synthetically induced Aquilaria malaccensis agarwoods
    Abdul Kadir FA, Azizan KA, Othman R
    Data Brief, 2020 Feb;28:104987.
    PMID: 32226799 DOI: 10.1016/j.dib.2019.104987
    Agarwood is the highly valuable fragrant resin of the wounded Aquilaria spp. trees widely used in fragrances, medicines and incenses. Among the Aquilaria spp., A. malaccensis is the primary producer and is mainly found in Indonesia and Malaysia. In normal condition, agarwood is naturally formed in Aquilaria trees as a defense mechanism upon physical damage or microbial infection on the trees, which is a slow process that occurs over several years. The high demand in agarwood has spurred the development of various artificial inoculation methods where agarwood formation is synthetically induced in a shorter period of time. However, the synthetic induction method produces agarwood with aromas different from the naturally formed agarwood. To understand the changes in the agarwoods produced from different induction conditions, metabolite profiling of agarwood essential oil from A. malaccensis has been performed. The essential oils of healthy undamaged tree trunks and, naturally formed and synthetically induced agarwoods were obtained using hydrodistillation (HS) method and analysed using gas chromatography mass spectrometer (GC-MS). These data will provide valuable resources for chemical components of agarwood produced by the species in the genus Aquilaria.
  18. Current approaches in antiviral drug discovery against the Flaviviridae family
    Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.
    Curr Pharm Des, 2014;20(21):3428-44.
    PMID: 24001228
    Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.
  19. Discovery of Dengue Virus Inhibitors
    Abdullah AA, Lee YK, Chin SP, Lim SK, Lee VS, Othman R, et al.
    Curr Med Chem, 2020;27(30):4945-5036.
    PMID: 30514185 DOI: 10.2174/0929867326666181204155336
    To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.
  20. Rational Drug Discovery of HCV Helicase Inhibitor: Improved Docking Accuracy with Multiple Seeding in AutoDock Vina and In Situ Minimization
    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.

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