Displaying publications 1 - 20 of 39 in total

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  1. Fulltext The viral capsid as novel nanomaterials for drug delivery
    Aljabali AA, Hassan SS, Pabari RM, Shahcheraghi SH, Mishra V, Charbe NB, et al.
    Future Sci OA, 2021 Oct;7(9):FSO744.
    PMID: 34737885 DOI: 10.2144/fsoa-2021-0031
    The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.
  2. Pharmacological advances in anti-retroviral therapy for human immunodeficiency virus-1 infection: A comprehensive review
    Azzman N, Gill MSA, Hassan SS, Christ F, Debyser Z, Mohamed WAS, et al.
    Rev Med Virol, 2024 Mar;34(2):e2529.
    PMID: 38520650 DOI: 10.1002/rmv.2529
    The discovery of anti-retroviral (ARV) drugs over the past 36 years has introduced various classes, including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitor, fusion, and integrase strand transfer inhibitors inhibitors. The introduction of combined highly active anti-retroviral therapies in 1996 was later proven to combat further ARV drug resistance along with enhancing human immunodeficiency virus (HIV) suppression. As though the development of ARV therapies was continuously expanding, the variation of action caused by ARV drugs, along with its current updates, was not comprehensively discussed, particularly for HIV-1 infection. Thus, a range of HIV-1 ARV medications is covered in this review, including new developments in ARV therapy based on the drug's mechanism of action, the challenges related to HIV-1, and the need for combination therapy. Optimistically, this article will consolidate the overall updates of HIV-1 ARV treatments and conclude the significance of HIV-1-related pharmacotherapy research to combat the global threat of HIV infection.
  3. Fulltext Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection
    Balasubramaniam VR, Wai TH, Omar AR, Othman I, Hassan SS
    Virol J, 2012;9:53.
    PMID: 22361110 DOI: 10.1186/1743-422X-9-53
    Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease (ND) viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses.
  4. Fulltext Cellular transcripts regulated during infections with Highly Pathogenic H5N1 Avian Influenza virus in 3 host systems
    Balasubramaniam VR, Hassan SS, Omar AR, Mohamed M, Noor SM, Mohamed R, et al.
    Virol J, 2011;8:196.
    PMID: 21529348 DOI: 10.1186/1743-422X-8-196
    Highly pathogenic Avian Influenza (HPAI) virus is able to infect many hosts and the virus replicates in high levels in the respiratory tract inducing severe lung lesions. The pathogenesis of the disease is actually the outcome of the infection as determined by complex host-virus interactions involving the functional kinetics of large numbers of participating genes. Understanding the genes and proteins involved in host cellular responses are therefore, critical for the elucidation of the mechanisms of infection.
  5. Detection of H5, H7 and H9 subtypes of avian influenza viruses by multiplex reverse transcription-polymerase chain reaction
    Chaharaein B, Omar AR, Aini I, Yusoff K, Hassan SS
    Microbiol Res, 2009;164(2):174-9.
    PMID: 17336046
    Subtype-specific multiplex reverse transcription-polymerase chain reaction (RT-PCR) was developed to simultaneously detect three subtypes (H5, H7 and H9) of avian influenza virus (AIV) type A. The sensitivity of the multiplex RT-PCR was evaluated and compared to that of RT-PCR-enzyme-linked immunosorbent assay (ELISA) and conventional RT-PCR. While the sensitivity of the multiplex RT-PCR is as sensitive as the conventional RT-PCR, it is 10 times less sensitive than RT-PCR-ELISA. The multiplex RT-PCR is also as sensitive as the virus isolation method in detecting H9N2 from tracheal samples collected at day 3 and 5 post inoculation. Hence, the developed multiplex RT-PCR assay is a rapid, sensitive and specific assay for detecting of AIV subtypes.
  6. Human neuronal cell protein responses to Nipah virus infection
    Chang LY, Ali AR, Hassan SS, AbuBakar S
    Virol J, 2007;4:54.
    PMID: 17553172
    Nipah virus (NiV), a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches.
  7. Nipah virus RNA synthesis in cultured pig and human cells
    Chang LY, Ali AR, Hassan SS, AbuBakar S
    J Med Virol, 2006 Aug;78(8):1105-12.
    PMID: 16789019
    Nipah virus infection of porcine stable kidney cells (PS), human neuronal cells (SK-N-MC), human lung fibroblasts cells (MRC-5), and human monocytes (THP-1) were examined. Rapid progression of cytopathic effects (CPE) and cell death were noted in PS cell cultures treated with Nipah virus, followed by MRC-5, SK-N-MC, and THP-1 cell cultures, in descending order of rapidity. Significant increase in the intracellular Nipah virus RNA occurred beginning at 24 hr PI in all the infected cells. Whereas, the extracellular release of Nipah virus RNA increased significantly beginning at 48 and 72 hr PI for the infected MRC-5 cells and PS cells, respectively. No significant release of extracellular Nipah virus RNA was detected from the Nipah virus-infected SK-N-MC and THP-1 cells. At its peak, approximately 6.6 log PFU/microl of extracellular Nipah virus RNA was released from the Nipah virus-infected PS cells, with at least a 100-fold less virus RNA was recorded in the Nipah virus-infected SK-N-MC and THP-1. Approximately 15.2% (+/-0.1%) of the released virus from the infected PS cell cultures was infectious in contrast to approximately 5.5% (+/-0.7%) from the infected SK-N-MC cells. The findings suggest that there are no differences in the capacity to support Nipah virus replication between pigs and humans in fully susceptible PS and MRC-5 cells. However, there are differences between these cells and human neuronal cells and monocytes in the ability to support Nipah virus replication and virus release.
  8. Quantitative estimation of Nipah virus replication kinetics in vitro
    Chang LY, Ali AR, Hassan SS, AbuBakar S
    Virol J, 2006;3:47.
    PMID: 16784519
    Nipah virus is a zoonotic virus isolated from an outbreak in Malaysia in 1998. The virus causes infections in humans, pigs, and several other domestic animals. It has also been isolated from fruit bats. The pathogenesis of Nipah virus infection is still not well described. In the present study, Nipah virus replication kinetics were estimated from infection of African green monkey kidney cells (Vero) using the one-step SYBR Green I-based quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.
  9. Fulltext Antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (GenBank accession no. MH488959)
    Chang YJ, Pong LY, Hassan SS, Choo WS
    Access Microbiol, 2020;2(1):acmi000073.
    PMID: 33062932 DOI: 10.1099/acmi.0.000073
    This study investigated the antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (DENV-2). The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by sub-fractionation and Amberlite XAD16N column chromatography to obtain betacyanin fractions. The half maximum cytotoxicity concentration for betacyanin fractions from red pitahaya and red spinach on Vero cells were 4.346 and 2.287 mg ml-1, respectively. The half-maximal inhibitory concentration (IC50) of betacyanin fraction from red pitahaya was 125.8 μg ml-1 with selectivity index (SI) of 5.8. For betacyanin fraction from red spinach, the IC50 value was 14.62 µg ml-1 with SI of 28.51. Using the maximum non-toxic betacyanin concentration, direct virucidal effect against DENV-2 was obtained from betacyanin fraction from red pitahaya (IC50 of 126.70 μg ml-1; 95.0 % virus inhibition) and red spinach (IC50 value of 106.80 μg ml-1; 65.9 % of virus inhibition). Betacyanin fractions from red pitahaya and red spinach inhibited DENV-2 in vitro.
  10. Fulltext Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection
    Dhanoa A, Fang NC, Hassan SS, Kaniappan P, Rajasekaram G
    Virol J, 2011;8:501.
    PMID: 22050645 DOI: 10.1186/1743-422X-8-501
    Numerous reports have described the epidemiological and clinical characteristics of influenza A (H1N1) 2009 infected patients. However, data on the effects of bacterial coinfection on these patients are very scarce. Therefore, this study explores the impact of bacterial coinfection on the clinical and laboratory parameters amongst H1N1 hospitalized patients.

    Study site: Hospital Sultanah Aminah Johor Bahru
  11. Risk factors and clinical outcome of profound thrombocytopenia in adult patients with DENV infections
    Dhanoa A, Rajasekaram G, Hassan SS, Ramadas A, Azreen Adnan NA, Lau CF, et al.
    Platelets, 2017 Nov;28(7):724-727.
    PMID: 28287000 DOI: 10.1080/09537104.2017.1293802
    Severe thrombocytopenia is common in dengue virus (DENV) infections. However, studies focusing on the role of profound thrombocytopenia (PT) (nadir platelet counts ≤ 20 000/mm3) in DENV infections are scarce. This study aims to identify the associated features and outcome of DENV patients with PT. It involves 237 adult hospitalized patients who were DENV PCR positive. The presence of comorbidity (AOR = 4.625; 95% CI = 1.113-19.230), higher admission hematocrit (AOR = 1.213; 95% CI = 1.067-1.379), lower admission albumin (AOR = 0.870; 95% CI = 0.766-0.988) and lower admission platelets (AOR = 0.980; 95% CI = 0.969-0.991) was associated with platelets ≤ 20 000/mm3 in multivariate logistic regression. PT was not affected by DENV serotypes, coinfections and secondary DENV infections. Patients with PT had significantly higher risk of experiencing warning signs (AOR = 3.709, 95% CI = 1.089-12.634) and longer hospital stay (AOR = 1.943, 95% CI = 1.010-3.774). However, severe dengue disease, hemorrhagic manifestations and need for intensive care were not significantly associated with PT.
  12. Fulltext Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters
    Dhanoa A, Hassan SS, Ngim CF, Lau CF, Chan TS, Adnan NA, et al.
    BMC Infect Dis, 2016 08 11;16(1):406.
    PMID: 27514512 DOI: 10.1186/s12879-016-1731-8
    BACKGROUND: The co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters.

    METHODS: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.

    RESULTS: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.

    CONCLUSION: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.

  13. Fulltext Contribution of Viral Respiratory Infections to Dengue-Like Illness Presentation at a Community Clinic in Southern Malaysia
    Dhanoa A, Ngim CF, Yunos NM, Husain SMT, Pong LY, Ismail WFW, et al.
    Am J Trop Med Hyg, 2021 Sep 27;106(1):187-191.
    PMID: 34583338 DOI: 10.4269/ajtmh.21-0648
    This study explored the contribution of viral respiratory infections (VRIs) in dengue-like illness (DLI) patients and their distinguishing clinicolaboratory parameters. Two hundred DLI patients were prospectively recruited (July 1- October 1, 2019) from a community clinic in Southern Malaysia. Patients ≥ 18 years with acute fever and fulfilling the WHO criteria of probable dengue were recruited. They underwent blood testing: blood counts, rapid dengue tests (nonstructural antigen-1/IgM) and polymerase chain reaction (PCR) for dengue, Zika, chikungunya, and Leptospira. Nasopharyngeal swabs (NPSs) were collected for FilmArray®RP2plus testing. From the 200 NPSs, 58 respiratory viruses (RVs) were detected in 54 patients. Of the 96 dengue-confirmed cases, 86 had dengue mono-infection, and 10 were coinfected with RVs. Of the 104 nondengue, 44 were RV positive and 4 Leptospira positive. Zika and chikungunya virus were not detected. Overall, the etiological diagnosis was confirmed for 72% of patients. Clinicolaboratory parameters were compared between dengue mono-infection and VRI mono-infection. Patients with coinfections were excluded. Multiple logistic regression showed that recent household/neighborhood history of dengue (adjusted odds ratio [aOR]: 5.9, 95% CI = 1.7-20.7), leukopenia (aOR: 12.5, 95% CI = 2.6-61.4) and thrombocytopenia (aOR: 5.5, 95% CI = 1.3-23.0) predicted dengue. Inversely, rhinorrhoea (aOR: 0.1, 95% CI = 0.01-0.3) and cough (aOR: 0.3, 95% CI = 0.1-0.9) favored VRI. Thus, VRIs comprise many infections diagnosed initially as DLIs. Early clinicolaboratory parameters can guide physicians screen patients for further testing.
  14. Fulltext Seroprevalence of dengue among healthy adults in a rural community in Southern Malaysia: a pilot study
    Dhanoa A, Hassan SS, Jahan NK, Reidpath DD, Fatt QK, Ahmad MP, et al.
    Infect Dis Poverty, 2018 Jan 16;7(1):1.
    PMID: 29335021 DOI: 10.1186/s40249-017-0384-1
    BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors.

    METHODS: In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database.

    RESULTS: The overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2% (31/277) of participants, whereas there was evidence of past infection in 75.5% (209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5% in the age group of <25 years to more than 85% in age group of >45 years (P 

  15. Feral cats and risk for Nipah virus transmission
    Epstein JH, Abdul Rahman S, Zambriski JA, Halpin K, Meehan G, Jamaluddin AA, et al.
    Emerg Infect Dis, 2006 Jul;12(7):1178-9.
    PMID: 16848051
  16. Evolution of HIV-1 reverse transcriptase and integrase dual inhibitors: Recent advances and developments
    Gill MSA, Hassan SS, Ahemad N
    Eur J Med Chem, 2019 Oct 01;179:423-448.
    PMID: 31265935 DOI: 10.1016/j.ejmech.2019.06.058
    HIV infection is a major challenge to mankind and a definitive cure or a viable vaccine for HIV is still elusive. HIV-1 is constantly evolving and developing resistant against clinically used anti-HIV drugs thus posing serious hurdles in the treatment of HIV infection. This prompts the need to developed new anti-HIV drugs; preferentially adopting intelligent ways to counteract an evolving virus. Highly Active Anti-Retroviral Therapy (HAART): a strategy involving multiple targeting through various drugs has proven beneficial in the management of AIDS. However, it is a complex regimen with high drug load, increased risk of drug interactions and adverse effects, which lead to poor patient compliance. Reverse transcriptase (RT) and Integrase (IN) are two pivotal enzymes in HIV-1 lifecycle with high structural and functional analogy to be perceived as drug-able targets for novel dual-purpose inhibitors. Designed multi-functional ligand (DML) is a modern strategy by which multiple targets can be exploited using a single chemical entity. A single chemical entity acting on multiple targets can be much more effective than a complex multi-drug regimen. The development of such multifunctional ligands is highly valued in anti-HIV drug discovery with the proposed advantage of being able to stop two or more stages of viral replication cycle. This review will encompass the evolution of the RT-IN dual inhibitory scaffolds reported so far and the contribution made by the leading research groups over the years in this field.
  17. Fulltext A green and efficient synthetic methodology towards the synthesis of 1-allyl-6-chloro-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives
    Gill MSA, Azzman N, Hassan SS, Shah SAA, Ahemad N
    BMC Chem, 2022 Dec 08;16(1):111.
    PMID: 36482476 DOI: 10.1186/s13065-022-00902-1
    Quinolone is a privileged scaffold in medicinal chemistry and 4-Quinolone-3-Carboxamides have been reported to harbor vast therapeutic potential. However, conversion of N-1 substituted 4-Quinolone 3-Carboxylate to its corresponding carbamates is highly restrictive. This motivated us to adopt a much simpler, scalable and efficient methodology for the synthesis of highly pure N-1 substituted 4- Quinolone-3-Carboxamides with excellent yields. Our adopted methodology not only provides a robust pathway for the convenient synthesis of N-1 substituted 4- Quinolone-3-Carboxamides which can then be explored for their therapeutic potential, this may also be adaptable for the derivatization of other such less reactive carboxylate species.
  18. Fulltext Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay
    Hariono M, Abdullah N, Damodaran KV, Kamarulzaman EE, Mohamed N, Hassan SS, et al.
    Sci Rep, 2016 12 20;6:38692.
    PMID: 27995961 DOI: 10.1038/srep38692
    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
  19. Fulltext Detection of neovascularization in diabetic retinopathy
    Hassan SS, Bong DB, Premsenthil M
    J Digit Imaging, 2012 Jun;25(3):437-44.
    PMID: 21901535 DOI: 10.1007/s10278-011-9418-6
    Diabetic retinopathy has become an increasingly important cause of blindness. Nevertheless, vision loss can be prevented from early detection of diabetic retinopathy and monitor with regular examination. Common automatic detection of retinal abnormalities is for microaneurysms, hemorrhages, hard exudates, and cotton wool spot. However, there is a worse case of retinal abnormality, but not much research was done to detect it. It is neovascularization where new blood vessels grow due to extensive lack of oxygen in the retinal capillaries. This paper shows that various combination of techniques such as image normalization, compactness classifier, morphology-based operator, Gaussian filtering, and thresholding techniques were used in developing of neovascularization detection. A function matrix box was added in order to classify the neovascularization from natural blood vessel. A region-based neovascularization classification was attempted as a diagnostic accuracy. The developed method was tested on images from different database sources with varying quality and image resolution. It shows that specificity and sensitivity results were 89.4% and 63.9%, respectively. The proposed approach yield encouraging results for future development.
  20. Cross Talk between MicroRNAs and Dengue Virus
    Macha NO, Komarasamy TV, Harun S, Adnan NAA, Hassan SS, Balasubramaniam VRMT
    Am J Trop Med Hyg, 2024 Apr 02.
    PMID: 38579704 DOI: 10.4269/ajtmh.23-0546
    Dengue fever (DF) is an endemic infectious tropical disease and is rapidly becoming a global problem. Dengue fever is caused by one of the four dengue virus (DENV) serotypes and is spread by the female Aedes mosquito. Clinical manifestations of DF may range from asymptomatic to life-threatening severe illness with conditions of hemorrhagic fever and shock. Early and precise diagnosis is vital to avoid mortality from DF. A different approach is required to combat DF because of the challenges with the vaccines currently available, which are nonspecific; each is capable of causing cross-reaction and disease-enhancing antibody responses against the residual serotypes. MicroRNAs (miRNAs) are known to be implicated in DENV infection and are postulated to be involved in most of the host responses. Thus, they might be a suitable target for new strategies against the disease. The involvement of miRNAs in cellular activities and pathways during viral infections has been explored under numerous conditions. Interestingly, miRNAs have also been shown to be involved in viral replication. In this review, we summarize the role of known miRNAs, specifically the role of miRNA Let-7c (miR-Let-7c), miR-133a, miR-30e, and miR-146a, in the regulation of DENV replication and their possible effects on the initial immune reaction.
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