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Violent crime datasets: Incidence and patterns in Malaysia from 2006 to 2017

Hakim HM, Khan HO, Hamzah HH, Othman MF, Nelson BR, Chambers GK, et al.

Data Brief, 2019 Oct;26:104449.
PMID: 31667222 DOI: 10.1016/j.dib.2019.104449

This article provides violent crime data in Malaysia from 2006 to 2017. The violent crimes include murder, rape, gang robbery, robbery and voluntarily causing hurt cases. A total of 330,395 violent crime cases were reported in this 12 year period and the data were tabulated state by state for all thirteen states of Malaysia, including two states in Borneo (Sabah and Sarawak) and one federal territory (Kuala Lumpur). In general, violent crimes show a decreasing trend from 2006 to 2017 in Malaysia. However, armed gang robbery and armed robbery show a fluctuating pattern from 2008 to 2011. A similar pattern was also recorded for unarmed gang robbery from 2008 to 2010. The violent crime data deposited here are available for further analysis, e.g., for identifying risk factors such as demography, lifestyle, socio-economic status, government policies etc. which may be associated with violent crime incidence and pattern across the country.
Fulltext Transfusion Medicine and Molecular Genetic Methods

Saleh RM, Zefarina Z, Che Mat NF, Chambers GK, Edinur HA

Int J Prev Med, 2018;9:45.
PMID: 29899883 DOI: 10.4103/ijpvm.IJPVM_232_16

Transfusion procedures are always complicated by potential genetic mismatching between donor and recipient. Compatibility is determined by several major antigens, such as the ABO and Rhesus blood groups. Matching for other blood groups (Kell, Kidd, Duffy, and MNS), human platelet antigens, and human leukocyte antigens (HLAs) also contributes toward the successful transfusion outcomes, especially in multitransfused or highly immunized patients. All these antigens of tissue identity are highly polymorphic and thus present great challenges for finding suitable donors for transfusion patients. The ABO blood group and HLA markers are also the determinants of transplant compatibility, and mismatched antigens will cause graft rejection or graft-versus-host disease. Thus, a single and comprehensive registry covering all of the significant transfusion and transplantation antigens is expected to become an important tool in providing an efficient service capable of delivering safe blood and quickly locating matching organs/stem cells. This review article is intended as an accessible guide for physicians who care for transfusion-dependent patients. In particular, it serves to introduce the new molecular screening methods together with the biology of these systems, which underlies the tests.
The genetic history of Peninsular Malaysia

Norhalifah HK, Syaza FH, Chambers GK, Edinur HA

Gene, 2016 Jul 15;586(1):129-35.
PMID: 27060406 DOI: 10.1016/j.gene.2016.04.008

This article explores the genetic history of the various sub-populations currently living in Peninsular Malaysia. This region has received multiple waves of migrants like the Orang Asli in prehistoric times and the Chinese, Indians, Europeans and Arabs during historic times. There are three highly distinct lineages that make up the Orang Asli; Semang, Senoi and Proto-Malays. The Semang, who have 'Negrito' characteristics, represent the first human settlers in Peninsular Malaysia arriving from about 50,000ya. The Senoi later migrated from Indochina and are a mix between an Asian Neolithic population and the Semang. These Asian genomes probably came in before Austroasiatic languages arrived between 5000 and 4000years ago. Semang and Senoi both now speak Austro-Asiatic languages indicative of cultural diffusion from Senoi to Semang. In contrast, the Proto-Malays who came last to the southern part of this region speak Austronesian language and are Austronesians with some Negrito admixture. It is from this group that the contemporary Malays emerged. Here we provide an overview of the best available genetic evidences (single nucleotide polymorphisms, mitochondrial DNA, Y-chromosome, blood groups, human platelet antigen, human leukocyte antigen, human neutrophil antigen and killer-cell immunoglobulin-like receptor) supporting the complex genetic history of Peninsular Malaysia. Large scale sampling and high throughput genetic screening programmes such as those using genome-wide single nucleotide polymorphism analyses have provided insights into various ancestral and admixture genetic fractions in this region. Given the now extensive admixture present in the contemporary descendants of ancient sub-populations in Peninsular Malaysia, improved reconstruction of human migration history in this region will require new evidence from ancient DNA in well-preserved skeletons. All other aspects of the highly diverse and complex genetic makeup in Peninsular Malaysia should be considered carefully for genetic mapping of disease loci and policy formation by health authorities.
Fulltext The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia

Tao S, Kichula KM, Harrison GF, Farias TDJ, Palmer WH, Leaton LA, et al.

Immunology, 2021 Apr;162(4):389-404.
PMID: 33283280 DOI: 10.1111/imm.13289

Killer cell immunoglobulin-like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune-mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under-represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+ HLA-C in the Malaysian Chinese group, caused by the low frequency of C2+ HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high-resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.
Fulltext The Prevalence of Transfusion-transmitted Infections among Blood Donors in Hospital Universiti Sains Malaysia

Ramli M, Zulkafli Z, Chambers GK, Zilan RSAR, Edinur HA

Oman Med J, 2020 Nov;35(6):e189.
PMID: 33110633 DOI: 10.5001/omj.2020.86

Objectives: Blood bank centers routinely screen for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) to ensure the safety of blood supply and thus prevent the dissemination of these viruses via blood transfusion. We sought to evaluate the detection of transfusion-transmitted infection (TTI) markers using standard serological methods and nucleic acid testing (NAT) among blood donors in Hospital Universiti Sains Malaysia.
Methods: Donated blood units were assessed for the presence or absence of HBV, HCV, and HIV using two screening method: serology and NAT. Reactive blood samples were then subjected to serological confirmatory and NAT discriminatory assays.
Results: A total of 9669 donors were recruited from September 2017 to June 2018. Among these, 36 donors were reactive either for HBV, HCV, or HIV by serological testing and eight by NAT screening. However, only 10 (three for HBV and seven for HCV) donors tested positive using serological testing and five (two for HBV and three for HCV) by NAT discriminatory assays. Note that all five NAT positive donors detected in the NAT discriminatory assays were confirmed to be serologically reactive. Therefore, the prevalence of HBV, HCV, and HIV was 0.03%, 0.1%, and 0.0%, respectively, in our donor pool.
Conclusions: Both serological and NAT screening and confirmatory assays should be used routinely to reduce the risk of infection transmission via the transfusion of blood and blood components.
Fulltext Synthesis and Characterization of Diosgenin Encapsulated Poly-ε-Caprolactone-Pluronic Nanoparticles and Its Effect on Brain Cancer Cells

Rabha B, Bharadwaj KK, Baishya D, Sarkar T, Edinur HA, Pati S

Polymers (Basel), 2021 Apr 18;13(8).
PMID: 33919483 DOI: 10.3390/polym13081322

Diosgenin encapsulated PCL-Pluronic nanoparticles (PCL-F68-D-NPs) were developed using the nanoprecipitation method to improve performance in brain cancer (glioblastoma) therapy. The nanoparticles were characterized by dynamic light scattering (DLS)/Zeta potential, Fourier-transform infrared (FTIR) spectra, X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), and Transmission electron microscopy (TEM). The encapsulation efficiency, loading efficiency, and yield were calculated. The in vitro release rate was determined, and the kinetic model of diosgenin release was plotted and ascertained. The cytotoxicity was checked by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)assay against U87-MG cells (glioblastoma cell lines). The obtained nanoparticles demonstrated good size distribution, stability, morphology, chemical, and mechanical properties. The nanoparticles also possessed high encapsulation efficiency, loading efficiency, and yield. The release rate of Diosgenin was shown in a sustained manner. The in vitro cytotoxicity of PCL-F68-D-NPs showed higher toxicity against U87-MG cells than free Diosgenin.
Fulltext Sri Petaling COVID-19 cluster in Malaysia: challenges and the mitigation strategies

Safuan S, Edinur HA

Acta Biomed, 2020 11 10;91(4):e2020154.
PMID: 33525245 DOI: 10.23750/abm.v91i4.10345

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Silencing E6/E7 Oncoproteins in SiHa Cells Treated with siRNAs and Oroxylum indicum Extracts Induced Apoptosis by Upregulating p53/pRb Pathways

Sisin NNT, Kong AR, Edinur HA, Jamil NIN, Che Mat NF

Appl Biochem Biotechnol, 2023 Nov 03.
PMID: 37922032 DOI: 10.1007/s12010-023-04762-w

E6 and E7 human papillomavirus (HPV) oncoproteins play a significant role in the malignant transformation of infected cervical cancer cells via suppression of tumour suppressor pathways by targeting p53 and pRb, respectively. This study aimed to investigate the anticancer effects of Oroxylum indicum (OI) leaves' methanol extract on SiHa cervical cancer cells. Expression of apoptosis-related proteins (Bcl-2, caspase (cas)-3, and cas-9), viral oncoproteins (E6 and E7), and tumour suppressor proteins (p53 and pRb) were evaluated using western blot analysis before and after E6/E7 small interfering RNAs (siRNAs) transfection. In addition, the E6/E7 mRNA expression levels were assessed with real-time (RT)-PCR. The present study showed that the OI extract effectively hindered the proliferation of SiHa cells and instigated increments of cas-3 and cas-9 expressions but decreased the Bcl-2 expressions. The OI extract inhibited E6/E7 viral oncoproteins, leading to upregulation of p53 and pRb tumour suppressor genes in SiHa cells. Additionally, combinatorial treatment of OI extract and gossypin flavonoid induced restorations of p53 and pRb. Treatment with OI extract in siRNA-transfected cells also further suppressed E6/E7 expression levels and further upregulations of p53 and pRb proteins. In conclusion, OI extract treatment on siRNAs-transfected SiHa cells can additively and effectively block E6- and E7-dependent p53 and pRb degradations. All these data suggest that OI could be explored for its chemotherapeutic potential in cervical cancer cells with HPV-integrated genomes.
Sequence polymorphisms of mtDNA HV1, HV2, and HV3 regions in the Malay population of Peninsular Malaysia

Nur Haslindawaty AR, Panneerchelvam S, Edinur HA, Norazmi MN, Zafarina Z

Int J Legal Med, 2010 Sep;124(5):415-26.
PMID: 20502908 DOI: 10.1007/s00414-010-0469-x

The uniparentally inherited mitochondrial DNA (mtDNA) is in the limelight for the past two decades, in studies relating to demographic history of mankind and in forensic kinship testing. In this study, human mtDNA hypervariable segments 1, 2, and 3 (HV1, HV2, and HV3) were analyzed in 248 unrelated Malay individuals in Peninsular Malaysia. Combined analyses of HV1, HV2, and HV3 revealed a total of 180 mtDNA haplotypes with 149 unique haplotypes and 31 haplotypes occurring in more than one individual. The genetic diversity was estimated to be 99.47%, and the probability of any two individuals sharing the same mtDNA haplotype was 0.93%. The most frequent mtDNA haplotype (73, 146, 150, 195, 263, 315.1C, 16140, 16182C, 16183C, 16189, 16217, 16274, and 16335) was shared by 11 (4.44%) individuals. The nucleotide diversity and mean of pair-wise differences were found to be 0.036063 ± 0.020101 and 12.544022 ± 6.230486, respectively.
Reconstruction of the Austronesian Diaspora in the Era of Genomics

Chambers GK, Edinur HA

Hum Biol, 2021 10;92(4):247-263.
PMID: 34665569 DOI: 10.13110/humanbiology.92.4.04

The Austronesian Diaspora is a 5,000-year account of how a small group of Taiwanese farmers expanded to occupy territories reaching halfway around the world. Reconstructing their detailed history has spawned many academic contests across many disciplines. An outline orthodox version has eventually emerged but still leaves many unanswered questions. The remarkable power of whole-genome technology has now been applied to people across the entire region. This review gives an account of this era of genetic investigation and discusses its many achievements, including revelation in detail of many unexpected patterns of population movement and the significance of this information for medical genetics.
Fulltext Recent Developments in Transplantation and Transfusion Medicine

Edinur HA, Chambers GK, Dunn PP

Ann. Transplant., 2015;20:424-9.
PMID: 26218888 DOI: 10.12659/AOT.894003

Transplantation and transfusion are related and clinically important areas of multidisciplinary expertise, including pre-operative treatment, donor recruitment, tissue matching, and post-operative care. We have seen significant developments in these areas, especially in the late 20th and early 21st century. This paper reviews the latest advances in modern transplantation and transfusion medicine, including several new genetic markers (e.g., major histocompatibility complex class I chain-related gene A, killer cell immunoglobulin-like receptor, and human platelet antigens) for donor and recipient matching, genotyping platforms (e.g., next-generation sequencer and Luminex technology), donor recruitment strategies, and several clinical applications in which genotyping has advantages over agglutination tests (e.g., genotyping of weakly expressed antigens and determination of blood groups and human leukocyte antigen types in multi-transfused patients). We also highlight the roles of population studies and international collaborations in moving towards more efficient donor recruitment strategies.
Fulltext Population dataset for 21 simple tandem repeat loci in the Akan population of Ghana

Kofi AE, Hakim HM, Khan HO, Ismail SA, Ghansah A, Haslindawaty ARN, et al.

Data Brief, 2020 Aug;31:105746.
PMID: 32490095 DOI: 10.1016/j.dib.2020.105746

Short tandem repeat (STR) loci are widely used as genetic marker for ancestral and forensic analyses. The latter application includes for paternity testing and DNA profiling of samples collected from scenes of crime and suspects. This survey provides the first dataset for 21 STR loci across the Akan population in Ghana by genotyping of 109 unrelated healthy individuals using Investigator 24plex kit. None of the STR loci screened deviated from Hardy-Weinberg equilibrium after applying Bonferroni correction. Overall, 224 unique alleles were observed with allele frequencies ranging from 0.005 to 0.518. The combined match probability, combined power of exclusion and combined power discrimination were 1 in 4.07 × 10-25, 0.999999999 and 1, respectively. Principal coordinate analysis carried out using 21 STR allele frequency data mapped the Akans with Nigerian subpopulation groups (Hausa, Igbo and Yoruba), but separated from Thais of Thailand, Chechen of Jordan and Tijuana of Mexico.
Population data of 23 Y chromosome STR loci for the five major human subpopulations of Ghana

Kofi AE, Hakim HM, Khan HO, Ismail SA, Ghansah A, David AA, et al.

Int J Legal Med, 2020 Jul;134(4):1313-1315.
PMID: 31154498 DOI: 10.1007/s00414-019-02099-w

In this study, 268 samples for unrelated males belonging to the five major human subpopulation groups in Ghana (Akan, Ewe, Mole-Dagbon, Ga-Dangme and Guang) were genetically characterised for 23 Y chromosome short tandem repeat (STR) loci using the Powerplex® Y23 STR kit. A total of 263 complete haplotypes were recorded of which 258 were unique. The haplotype diversity, discriminating capacity and match probability for the pooled population data were 0.9998, 0.9627 and 0.0039, respectively. The pairwise genetic distance (RST) for the Ghanaian datasets and other reference populations deposited in the Y-STR Haplotype Reference Database (YHRD) were estimated and mapped using multidimensional scaling (MDS) plot. The Guang and Ewe were significantly different from the Akan, Mole-Dagbon and Ga-Dangme. However, the five Ghanaian datasets were all plotted close together with other African populations in the MDS data mapping.
Population data for 23 Y chromosome STR loci using the Powerplex® Y23 STR kit for the Kedayan population in Malaysia

Hakim HM, Khan HO, Ismail SA, Lalung J, Kofi AE, Nelson BR, et al.

Int J Legal Med, 2020 Jul;134(4):1335-1337.
PMID: 31897667 DOI: 10.1007/s00414-019-02237-4

Genetic polymorphisms at 23 Y chromosome short tandem repeat (STRs) loci included in the Powerplex® Y23 PCR kit were successfully scored in 128 unrelated Kedayan individuals living in Sabah, East Malaysia. Complete haplotypes were recorded for all individuals and included 92 different types with 72 being unique to single male subjects. Three important forensic statistics were calculated from these data; haplotype diversity = 0.993, discriminating capacity = 0.719, and match probability = 0.015. The Kedayan appear to be most closely related to Malays and Filipinos in a multidimensional scaling plot and are separated from other mainland Asia populations including Thais and Hakka Han. These new data for Kedayan have been deposited in the YHRD database (accession number: YA004621). Our statistical analyses showed the reliability of Y-STR loci for geographically extended use in forensic casework and for studying human population history.
Population data and genetic characteristics of 12 X-STR loci using the Investigator® Argus X-12 Quality Sensor kit for the Kedayan population of Borneo in Malaysia

Hakim HM, Khan HO, Ismail SA, Lalung J, Kofi AE, Aziz MY, et al.

Int J Legal Med, 2021 Jul;135(4):1433-1435.
PMID: 33782746 DOI: 10.1007/s00414-021-02577-0

DNA profiling of X-chromosomal short tandem repeats (X-STR) has exceptional value in criminal investigations, especially for complex kinship and incest cases. In this study, Investigator® Argus X-12 Quality Sensor (QS) kits were successfully used to characterize 12 X-STR loci in 199 unrelated healthy Kedayan individuals living in Sabah and Sarawak, Malaysia. The LG1 haplogroup (DXS8378 - DXS10135 - DXS10148) has the largest HD (0.9799) as compared with all other closely linked haplotype groups examined (LG2; DXS7132-DXS10074-DXS10079, LG3; DXS10103-DXS10101-HPRTB and LG4; DXS10134-DXS7423-DXS10146). Data from statistical analysis showed that high combined of PDM, PDF, MEC_Krüger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_duo values (0.999999994405922, 0.99999999999999, 0.999990463834938, 0.999999975914808, 0.999999975985006, and 0.999996491927194, respectively) in the Kedayan. In a two-dimensional scaling (MDS) plot and dendrogram constructed using allele frequencies at the 12 X-STR loci, Kedayan appear to be most closely related to their other Austronesian populations including the Malays and Filipinos as compared with other reference population groups. Findings from the present study thus demonstrate high genetic variability across the 12 tested X-STR loci and can be used for population studies and forensic applications.
Molecular blood group typing in Banjar, Jawa, Mandailing and Kelantan Malays in Peninsular Malaysia

Abd Gani R, Manaf SM, Zafarina Z, Panneerchelvam S, Chambers GK, Norazmi MN, et al.

Transfus Apher Sci, 2015 Aug;53(1):69-73.
PMID: 25819336 DOI: 10.1016/j.transci.2015.03.009

In this study we genotyped ABO, Rhesus, Kell, Kidd and Duffy blood group loci in DNA samples from 120 unrelated individuals representing four Malay subethnic groups living in Peninsular Malaysia (Banjar: n = 30, Jawa: n = 30, Mandailing: n = 30 and Kelantan: n = 30). Analyses were performed using commercial polymerase chain reaction-sequence specific primer (PCR-SSP) typing kits (BAG Health Care GmbH, Lich, Germany). Overall, the present study has successfully compiled blood group datasets for the four Malay subethnic groups and used the datasets for studying ancestry and health.
Fulltext Microbiologically-Synthesized Nanoparticles and Their Role in Silencing the Biofilm Signaling Cascade

Lahiri D, Nag M, Sheikh HI, Sarkar T, Edinur HA, Pati S, et al.

Front Microbiol, 2021;12:636588.
PMID: 33717030 DOI: 10.3389/fmicb.2021.636588

The emergence of bacterial resistance to antibiotics has led to the search for alternate antimicrobial treatment strategies. Engineered nanoparticles (NPs) for efficient penetration into a living system have become more common in the world of health and hygiene. The use of microbial enzymes/proteins as a potential reducing agent for synthesizing NPs has increased rapidly in comparison to physical and chemical methods. It is a fast, environmentally safe, and cost-effective approach. Among the biogenic sources, fungi and bacteria are preferred not only for their ability to produce a higher titer of reductase enzyme to convert the ionic forms into their nano forms, but also for their convenience in cultivating and regulating the size and morphology of the synthesized NPs, which can effectively reduce the cost for large-scale manufacturing. Effective penetration through exopolysaccharides of a biofilm matrix enables the NPs to inhibit the bacterial growth. Biofilm is the consortia of sessile groups of microbial cells that are able to adhere to biotic and abiotic surfaces with the help extracellular polymeric substances and glycocalyx. These biofilms cause various chronic diseases and lead to biofouling on medical devices and implants. The NPs penetrate the biofilm and affect the quorum-sensing gene cascades and thereby hamper the cell-to-cell communication mechanism, which inhibits biofilm synthesis. This review focuses on the microbial nano-techniques that were used to produce various metallic and non-metallic nanoparticles and their "signal jamming effects" to inhibit biofilm formation. Detailed analysis and discussion is given to their interactions with various types of signal molecules and the genes responsible for the development of biofilm.
Fulltext Microbial Fabrication of Nanomaterial and Its Role in Disintegration of Exopolymeric Matrices of Biofilm

Nag M, Lahiri D, Sarkar T, Ghosh S, Dey A, Edinur HA, et al.

Front Chem, 2021;9:690590.
PMID: 34109159 DOI: 10.3389/fchem.2021.690590

Bacterial biofilms are responsible for the development of various chronic wound-related and implant-mediated infections and confer protection to the pathogenic bacteria against antimicrobial drugs and host immune responses. Hence, biofilm-mediated chronic infections have created a tremendous burden upon healthcare systems worldwide. The development of biofilms upon the surface of medical implants has resulted in the failure of various implant-based surgeries and therapies. Although different conventional chemical and physical agents are used as antimicrobials, they fail to kill the sessile forms of bacterial pathogens due to the resistance exerted by the exopolysaccharide (EPS) matrices of the biofilm. One of the major techniques used in addressing such a problem is to directly check the biofilm formation by the use of novel antibiofilm materials, local drug delivery, and device-associated surface modifications, but the success of these techniques is still limited. The immense expansion in the field of nanoscience and nanotechnology has resulted in the development of novel nanomaterials as biocidal agents that can be either easily integrated within biomaterials to prevent the colonization of microbial cells or directly approach the pathogen overcoming the biofilm matrix. The antibiofilm efficacies of these nanomaterials are accomplished by the generation of oxidative stresses and through alterations of the genetic expressions. Microorganism-assisted synthesis of nanomaterials paved the path to success in such therapeutic approaches and is found to be more acceptable for its "greener" approach. Metallic nanoparticles functionalized with microbial enzymes, silver-platinum nanohybrids (AgPtNHs), bacterial nanowires, superparamagnetic iron oxide (Fe3O4), and nanoparticles synthesized by both magnetotactic and non-magnetotactic bacteria showed are some of the examples of such agents used to attack the EPS.
Fulltext Mannose-binding lectin gene sequence data in Kelantan population

Zahidin MA, Mohd Noor NH, Johan MF, Abdullah AD, Zulkafli Z, Edinur HA

Sci Data, 2024 Apr 30;11(1):435.
PMID: 38688916 DOI: 10.1038/s41597-024-03274-4

The human mannose-binding lectin (MBL) gene encodes a polymorphic protein that plays a crucial role in the innate immune response. Human MBL deficiency is associated with immunodeficiencies, and its variants have been linked to autoimmune and infectious diseases. Despite this significance, gene studies concerning MBL sequencing are uncommon in Malaysia. Therefore, we aimed to preliminary described the human MBL sequencing dataset based on the Kelantan population. Blood samples were collected from 30 unrelated individuals and underwent DNA extraction, genotyping, and sequencing. The sequencing data generated 886 bp, which were deposited in GenBank (ON619541-ON619546). Allelic variants were identified and translated into six MBL haplotypes: HYPA, HYPB, LYPB, LXPB, HXPA, and LXPA. An evolutionary tree was constructed using the haplotype sequences. These findings contribute to the expansion of MBL information within the country, providing a valuable baseline for future research exploring the association between the gene and targeted diseases.
Fulltext Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 Mpro: Bioinformatics Approach

Bharadwaj KK, Sarkar T, Ghosh A, Baishya D, Rabha B, Panda MK, et al.

Appl Biochem Biotechnol, 2021 Oct;193(10):3371-3394.
PMID: 34212286 DOI: 10.1007/s12010-021-03608-7

COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski's rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of -9.22 and -8.00 kcal/mol, respectively, within the binding pocket of the Mpro catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of Mpro-Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems.

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