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Fulltext Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design

Chong LC, Khan AM

BMC Genomics, 2019 Dec 24;20(Suppl 9):921.
PMID: 31874646 DOI: 10.1186/s12864-019-6311-z

BACKGROUND: The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome.
METHODS: All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database.
RESULTS: A total of 2321 nonamers met the HCSS selection criteria of entropy 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity.
CONCLUSION: This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.
Fulltext Correction to: Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design

Chong LC, Khan AM

BMC Genomics, 2021 Mar 26;22(1):219.
PMID: 33771112 DOI: 10.1186/s12864-021-07444-1
Fulltext Historical milestone in 42 years of viral sequencing-Impetus for a community-driven sequencing of global priority pathogens

Chong LC, Khan AM

Front Microbiol, 2022;13:1020148.
PMID: 36406392 DOI: 10.3389/fmicb.2022.1020148
Seasonal changes in the prevalence of Haemonchus and Trichostrongylus hypobiotic larvae in tracer goats in Malaysia

Ikeme MM, Iskander F, Chong LC

Trop Anim Health Prod, 1987 Aug;19(3):184-90.
PMID: 3660455

An investigation into the seasonal changes in the population structure of Haemonchus and Trichostrongylus in tracer goats was conducted over 12 months at Serdang, an area in southern West Malaysia with year-round tropical rainfall. Successive groups of parasite-free tracer goats were grazed for a month alongside naturally infected adult goats and necropsied for worm counts 14 days after their removal from pasture. No hypobiotic larvae of Trichostrongylus were recovered. Hypobiotic larvae of Haemonchus were evident during each month of the year but accounted for only a very small proportion of the total Haemonchus burden. Very low levels were encountered from December through to June. Comparatively higher levels of hypobiosis were observed thereafter with a peak of 7.4% in September. The factors responsible for hypobiosis were not clearly defined but the phenomenon was associated with increasing levels of soil moisture storage. Host resistance, adult worm population of tracers and population of ingested L3 were ruled out as possible inducing factors.
Chemical composition and physicochemical properties of green banana (Musa acuminata x balbisiana Colla cv. Awak) flour

Haslinda WH, Cheng LH, Chong LC, Noor Aziah AA

Int J Food Sci Nutr, 2009;60 Suppl 4:232-9.
PMID: 19449278 DOI: 10.1080/09637480902915525

Flour was prepared from peeled and unpeeled banana Awak ABB. Samples prepared were subjected to analysis for determination of chemical composition, mineral, dietary fibre, starch and total phenolics content, antioxidant activity and pasting properties. In general, flour prepared from unpeeled banana was found to show enhanced nutrition values with higher contents of mineral, dietary fibre and total phenolics. Hence, flour fortified with peel showed relatively higher antioxidant activity. On the other hand, better pasting properties were shown when banana flour was blended with peel. It was found that a relatively lower pasting temperature, peak viscosity, breakdown, final viscosity and setback were evident in a sample blended with peel.
Fulltext Expression, purification and characterization of the dimeric protruding domain of Macrobrachium rosenbergii nodavirus capsid protein expressed in Escherichia coli

Chong LC, Ganesan H, Yong CY, Tan WS, Ho KL

PLoS One, 2019;14(2):e0211740.
PMID: 30707739 DOI: 10.1371/journal.pone.0211740

Macrobrachium rosenbergii nodavirus (MrNV) is the causative agent of white tail disease (WTD) which seriously impedes the production of the giant freshwater prawn and has a major economic impact. MrNV contains two segmented RNA molecules, which encode the RNA dependent RNA polymerase (RdRp) and the capsid protein (MrNV-CP) containing 371 amino acid residues. MrNV-CP comprises of the Shell (S) and the Protruding (P) domains, ranging from amino acid residues 1-252 and 253-371, respectively. The P-domain assembles into dimeric protruding spikes, and it is believed to be involved in host cell attachment and internalization. In this study, the recombinant P-domain of MrNV-CP was successfully cloned and expressed in Escherichia coli, purified with an immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC) up to ~90% purity. Characterization of the purified recombinant P-domain with SEC revealed that it formed dimers, and dynamic light scattering (DLS) analysis demonstrated that the hydrodynamic diameter of the dimers was ~6 nm. Circular dichroism (CD) analysis showed that the P-domain contained 67.9% of beta-sheets, but without alpha-helical structures. This is in good agreement with the cryo-electron microscopic analysis of MrNV which demonstrated that the P-domain contains only beta-stranded structures. Our findings of this study provide essential information for the production of the P-domain of MrNV-CP that will aid future studies particularly studies that will shed light on anti-viral drug discovery and provide an understanding of virus-host interactions and the viral pathogenicity.
Fulltext Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB

Int J Mol Sci, 2021 Aug 20;22(16).
PMID: 34445667 DOI: 10.3390/ijms22168962

Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.
Fatty acid profile, minor bioactive constituents and physicochemical properties of insect-based oils: A comprehensive review

Yap JW, Lee YY, Tang TK, Chong LC, Kuan CH, Lai OM, et al.

Crit Rev Food Sci Nutr, 2023;63(21):5231-5246.
PMID: 34913758 DOI: 10.1080/10408398.2021.2015681

Insect-based food or ingredients have received tremendous attention worldwide because of their potential to ensure food and nutrition security, mitigating the reliance on land-dependent agricultural products. Indeed, insect-farming has low environmental impacts with reduced land, water and energy input. More importantly, insects are rich in high quality proteins and fats. They are also excellent sources of minerals, vitamins and bioactive compounds. Insect-based lipids are intriguing because they may contain high levels of unsaturated fatty acids particularly linoleic and α-linolenic acids. Besides, the insect-based lipids also show a considerable amount of bioactive components such as tocols, sterols and carotenoids. However, their fatty acid compositions and the nutritional values may vary depending on species, feed composition, developmental stage, geographical locations, and extraction techniques. Therefore, the present article aims to provide a comprehensive review on the fatty acid composition, the minor bioactive constituents and the physicochemical properties of fats and oils derived from insects of different orders (Coleoptera, Lepidoptera, Hymenoptera, Orthoptera, Hemiptera and Diptera). The various parameters affecting the nutritional compositions of the insect-based lipids will also be highlighted. These information will definitely provide a detailed insight on the potential applications of these fats in various food systems based on their unique properties.
Genomic analysis and biological characterization of a novel Schitoviridae phage infecting Vibrio alginolyticus

Tajuddin S, Khan AM, Chong LC, Wong CL, Tan JS, Ina-Salwany MY, et al.

Appl Microbiol Biotechnol, 2023 Feb;107(2-3):749-768.
PMID: 36520169 DOI: 10.1007/s00253-022-12312-3

Vibrio alginolyticus is a Gram-negative bacterium commonly associated with mackerel poisoning. A bacteriophage that specifically targets and lyses this bacterium could be employed as a biocontrol agent for treating the bacterial infection or improving the shelf-life of mackerel products. However, only a few well-characterized V. alginolyticus phages have been reported in the literature. In this study, a novel lytic phage, named ΦImVa-1, specifically infecting V. alginolyticus strain ATCC 17749, was isolated from Indian mackerel. The phage has a short latent period of 15 min and a burst size of approximately 66 particles per infected bacterium. ΦImVa-1 remained stable for 2 h at a wide temperature (27-75 °C) and within a pH range of 5 to 10. Transmission electron microscopy revealed that ΦImVa-1 has an icosahedral head of approximately 60 nm in diameter with a short tail, resembling those in the Schitoviridae family. High throughput sequencing and bioinformatics analysis elucidated that ΦImVa-1 has a linear dsDNA genome of 77,479 base pairs (bp), with a G + C content of ~ 38.72% and 110 predicted gene coding regions (106 open reading frames and four tRNAs). The genome contains an extremely large virion-associated RNA polymerase gene and two smaller non-virion-associated RNA polymerase genes, which are hallmarks of schitoviruses. No antibiotic genes were found in the ΦImVa-1 genome. This is the first paper describing the biological properties, morphology, and the complete genome of a V. alginolyticus-infecting schitovirus. When raw mackerel fish flesh slices were treated with ΦImVa-1, the pathogen loads reduced significantly, demonstrating the potential of the phage as a biocontrol agent for V. alginolyticus strain ATCC 17749 in the food. KEY POINTS: • A novel schitovirus infecting Vibrio alginolyticus ATCC 17749 was isolated from Indian mackerel. • The complete genome of the phage was determined, analyzed, and compared with other phages. • The phage is heat stable making it a potential biocontrol agent in extreme environments.