Displaying publications 1 - 20 of 83 in total

  1. 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.
    Matched MeSH terms: Viral Nonstructural Proteins
  2. Zin K, Morita K, Igarashi A
    Microbiol. Immunol., 1995;39(8):581-90.
    PMID: 7494497
    We determined the 240-nucleotide sequences of the E/NS1 gene junction of four dengue-2 viruses by the primer extension dideoxy chain termination method. These viruses were isolated from dengue patients with different clinical severities in Nakhon Phanom, Northeastern Thailand in 1993. The results were compared with the 52 published dengue-2 sequences of the same gene region. Sequence divergence of four new isolates varied from 4.17% to 5.42% compared with dengue-2 prototype New Guinea C strain whereas it varied from 5.42% to 6.67% and from 6.67% to 7.09% when compared with Jamaica 1409 strain and PR159/S1 strain, respectively. All nucleotide substitutions were found at the 3rd position of the codons which were silent mutations. All 56 isolates studied were classified into five genotypic groups by constructing the dendrogram. The results indicated that four new isolates from Northeastern Thailand belong to genotype II of dengue virus serotype 2, and were most closely related to prototype New Guinea C strain. We also observed the variation in nucleotide and amino acid sequences among clusters of isolates (Thailand-1980, Malaysia-1989 and Thailand-1993) which were obtained from the dengue patients with different clinical severities. The significance of these genetic differences have been discussed in terms of the possible correlation between genetic variability and virulence.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics*
  3. Lau SM, Chua TH, Sulaiman WY, Joanne S, Lim YA, Sekaran SD, et al.
    Parasit Vectors, 2017 Mar 21;10(1):151.
    PMID: 28327173 DOI: 10.1186/s13071-017-2091-y
    BACKGROUND: Dengue remains a serious public health problem in Southeast Asia and has increased 37-fold in Malaysia compared to decades ago. New strategies are urgently needed for early detection and control of dengue epidemics.

    METHODS: We conducted a two year study in a high human density dengue-endemic urban area in Selangor, where Gravid Ovipositing Sticky (GOS) traps were set up to capture adult Aedes spp. mosquitoes. All Aedes mosquitoes were tested using the NS1 dengue antigen test kit. All dengue cases from the study site notified to the State Health Department were recorded. Weekly microclimatic temperature, relative humidity (RH) and rainfall were monitored.

    RESULTS: Aedes aegypti was the predominant mosquito (95.6%) caught in GOS traps and 23% (43/187 pools of 5 mosquitoes each) were found to be positive for dengue using the NS1 antigen kit. Confirmed cases of dengue were observed with a lag of one week after positive Ae. aegypti were detected. Aedes aegypti density as analysed by distributed lag non-linear models, will increase lag of 2-3 weeks for temperature increase from 28 to 30 °C; and lag of three weeks for increased rainfall.

    CONCLUSION: Proactive strategy is needed for dengue vector surveillance programme. One method would be to use the GOS trap which is simple to setup, cost effective (below USD 1 per trap) and environmental friendly (i.e. use recyclable plastic materials) to capture Ae. aegypti followed by a rapid method of detecting of dengue virus using the NS1 dengue antigen kit. Control measures should be initiated when positive mosquitoes are detected.

    Matched MeSH terms: Viral Nonstructural Proteins/analysis*; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/immunology
  4. Kumarasamy V, Chua SK, Hassan Z, Wahab AH, Chem YK, Mohamad M, et al.
    Singapore Med J, 2007 Jul;48(7):669-73.
    PMID: 17609831
    INTRODUCTION: The aim of this report is to establish an accurate diagnosis of acute dengue virus infection early, in order to provide timely information for the management of patients and early public health control of dengue outbreak.
    METHODS: 224 serum samples from patients with a clinical diagnosis of acute dengue infection, which were subsequently confirmed by laboratory tests, were used to evaluate the performance of a commercially-available dengue NS1 antigen-capture ELISA kit.
    RESULTS: The dengue NS1 antigen-capture ELISA gave an overall sensitivity rate of 93.3 percent (209/224). The sensitivity rate was significantly higher in acute primary dengue (97.4 percent) than in acute secondary dengue (68.8 percent). In comparison, the virus isolation gave an overall positive isolation rate of 64.7 percent, with a positive rate of 70.8 percent and 28.1 percent, for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 63.4 percent, with a positive rate of 62.5 percent and 68.8 percent, for acute primary dengue and acute secondary dengue, respectively. Of the 224 acute serum samples from patients with laboratory-confirmed acute dengue infection, dengue IgM was detected in 88 specimens, comprising 68 acute primary dengue specimens and 20 acute secondary dengue specimens. NS1 antigen-capture ELISA kit gave an overall sensitivity rate of 88.6 percent in the presence of anti-dengue IgM and 96.3 percent in the absence of anti-dengue IgM.
    CONCLUSION: Of the 224 acute serum samples, the sample ages of 166 acute serum samples are known. The positive detection rate of dengue NS1 antigen-capture ELISA, on the whole, was higher than the other three established diagnostic test methods for laboratory diagnosis of acute dengue infection.
    Matched MeSH terms: Viral Nonstructural Proteins/blood*; Viral Nonstructural Proteins/immunology
  5. Chong HY, Leow CY, Leow CH
    Int J Biol Macromol, 2021 Aug 31;185:485-493.
    PMID: 34174313 DOI: 10.1016/j.ijbiomac.2021.06.146
    Co-existence of Japanese Encephalitis virus (JEV) with highly homologous antigenic epitopes results in antibody-based serodiagnosis being inaccurate at detecting and distinguishing JEV from other flaviviruses. This often causes misdiagnosis and inefficient treatments of flavivirus infection. Generation of JEV NS1 protein remains a challenge as it is notably expressed in the form of inactive aggregates known as inclusion bodies using bacterial expression systems. This study evaluated two trxB and gor E. coli strains in producing soluble JEV NS1 via a cold-shock expression system. High yield of JEV NS1 inclusion bodies was produced using cold-shocked expression system. Subsequently, a simplified yet successful approach in generating soluble, active JEV NS1 protein through solubilization, purification and in vitro refolding of JEV NS1 protein from inclusion bodies was developed. A step-wise dialysis refolding approach was used to facilitate JEV NS1 refolding. The authenticity of the refolded JEV NS1 was confirmed by specific antibody binding on indirect ELISA commercial anti-NS1 antibodies which showed that the refolded JEV NS1 was highly immunoreactive. This presented approach is cost-effective, and negates the need for mammalian or insect cell expression systems in order to synthesize this JEV NS1 protein of important diagnostic and therapeutic relevance in Japanese Encephalitis disease.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics*; Viral Nonstructural Proteins/immunology; Viral Nonstructural Proteins/metabolism; Viral Nonstructural Proteins/chemistry
  6. Seyedi SS, Shukri M, Hassandarvish P, Oo A, Shankar EM, Abubakar S, et al.
    Sci Rep, 2016 04 13;6:24027.
    PMID: 27071308 DOI: 10.1038/srep24027
    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya infection in humans. Despite the widespread distribution of CHIKV, no antiviral medication or vaccine is available against this virus. Therefore, it is crucial to find an effective compound to combat CHIKV. We aimed to predict the possible interactions between non-structural protein 3 (nsP) of CHIKV as one of the most important viral elements in CHIKV intracellular replication and 3 potential flavonoids using a computational approach. The 3-dimensional structure of nsP3 was retrieved from the Protein Data Bank, prepared and, using AutoDock Vina, docked with baicalin, naringenin and quercetagetin as ligands. The first-rated ligand with the strongest binding affinity towards the targeted protein was determined based on the minimum binding energy. Further analysis was conducted to identify both the active site of the protein that reacts with the tested ligands and all of the existing intermolecular bonds. Compared to the other ligands, baicalin was identified as the most potential inhibitor of viral activity by showing the best binding affinity (-9.8 kcal/mol). Baicalin can be considered a good candidate for further evaluation as a potentially efficient antiviral against CHIKV.
    Matched MeSH terms: Viral Nonstructural Proteins/metabolism; Viral Nonstructural Proteins/chemistry*
  7. Chow VT, Seah CL, Chan YC
    Intervirology, 1994;37(5):252-8.
    PMID: 7698880
    By a combination of PCR and direct-cycle sequencing using consensus primers, we analyzed approximately 400-bp fragments within the NS3 genes of twenty-one dengue virus type 3 strains isolated from five neighboring Southeast Asian countries at different time intervals from 1956 to 1992. The majority of base disparities were silent mutations, with few predicted amino acid substitutions, thus emphasizing the strict conservation of the NS3 gene. Phylogenetic trees constructed on the basis of these nucleotide differences revealed distinct but related clusters of strains from the Philippines, Indonesia, and strains from Singapore and Malaysia of the 1970s and early 1980s, while the Thai cluster was relatively more distant. This genetic relationship was compatible with that proposed by other workers who have studied other dengue 3 virus genes such as E, M and prM. However, we observed that the more recent, epidemic-associated dengue 3 strains from Singapore and Malaysia of the late 1980s and early 1990s were more closely related to the Thai cluster, implying their evolution from the latter, and emphasizing the importance of viral spread via increasing travel within the Southeast Asian area and elsewhere. Nucleotide sequence analysis of the NS3 genes of dengue viruses can serve to advance the understanding of the epidemiology and evolution of these viruses.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics*; Viral Nonstructural Proteins/chemistry
  8. Tan TS, Syed Hassan S, Yap WB
    Lett Appl Microbiol, 2017 Jun;64(6):446-451.
    PMID: 28370088 DOI: 10.1111/lam.12738
    The study aimed to construct a recombinant Lactobacillus casei expressing the nonstructural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by Lact. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in Lact. casei. The plasmid was stably maintained (98·94 ± 1·65%) by the bacterium within the first 20 generations without selective pressure. The NS1 was expressed as a 49-kDa protein in association with the anchoring peptide. The yield was 1·325 ± 0·065 μg mg(-1) of bacterial cells. Lactobacillus casei expressing the NS1 on its cell wall was red-fluorescently stained, but the staining was not observed on Lact. casei carrying the empty pSGANC332. The results implied that Lact. casei strain C1 is a promising host for the expression of surface-bound NS1 protein using the pSGANC332 expression plasmid.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The study has demonstrated, for the first time, the expression of nonstructural 1 (NS1) protein of influenza A virus H5N1 on the cell wall of Lactobacillus casei using the pSGANC332 expression plasmid. Display of NS1 protein on the bacterial cell wall was evident under an immunofluorescence microscopic observation. Lactobacillus casei carrying the NS1 protein could be developed into a universal oral influenza vaccine since the NS1 is highly conserved among influenza viruses.

    Matched MeSH terms: Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism*
  9. Aw-Yong KL, Sam IC, Koh MT, Chan YF
    PLoS One, 2016;11(11):e0165659.
    PMID: 27806091 DOI: 10.1371/journal.pone.0165659
    Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142-156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41-55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/immunology*
  10. Zainah S, Wahab AH, Mariam M, Fauziah MK, Khairul AH, Roslina I, et al.
    J Virol Methods, 2009 Feb;155(2):157-60.
    PMID: 19022293 DOI: 10.1016/j.jviromet.2008.10.016
    The performance of a commercial immunochromatography test for rapid detection of dengue NS1 antigen present in serum or plasma of patients was evaluated against a commercial dengue NS1 antigen-capture ELISA. The rapid immunochromatography test gave an overall sensitivity of 90.4% with a specificity of 99.5%. The sensitivity was highest for serum samples from which virus was isolated (96.3%) and lowest for those from which virus was not isolated and RT-PCR was negative (76.4%). The sensitivity was significantly higher for serum samples from patients with acute primary dengue (92.3%) than those from patients with acute secondary dengue (79.1%). The positive predictive value and negative predictive value of this commercial immunochromatography test were 99.6% and 87.9% respectively.
    Matched MeSH terms: Viral Nonstructural Proteins/blood*; Viral Nonstructural Proteins/immunology
  11. Norazharuddin H, Lai NS
    Malays J Med Sci, 2018 Sep;25(5):6-15.
    PMID: 30914859 DOI: 10.21315/mjms2018.25.5.2
    Dengue is a neglected disease caused by the infection of dengue virus which is transmitted by Aedes mosquitoes and to some, it could be fatal. Regardless of the enormous work devoted to research for the treatment of dengue, to this day there is no cure, and treatment is solely limited to supportive care by treating the symptoms. The inhibition of the viral RNA non-structural enzymes has been the most popular approach amongst the strategies applied to the search and development of dengue antivirals. This review is a compact digest of what is already known of the roles and the prospects of the dengue virus non-structural proteins NS1, NS2BNS3, NS4A, NS4B and NS5 as the targets for antiviral studies including the recent progress that has been published regarding their roles.
    Matched MeSH terms: Viral Nonstructural Proteins
  12. Chong Teoh T, J Al-Harbi S, Abdulrahman AY, Rothan HA
    Molecules, 2021 Jul 16;26(14).
    PMID: 34299596 DOI: 10.3390/molecules26144321
    Zika virus (ZIKV) represents a re-emerging threat to global health due to its association with congenital birth defects. ZIKV NS2B-NS3 protease is crucial for virus replication by cleaving viral polyprotein at various junctions to release viral proteins and cause cytotoxic effects in ZIKV-infected cells. This study characterized the inhibitory effects of doxycycline against ZIKV NS2B-NS3 protease and viral replication in human skin cells. The in silico data showed that doxycycline binds to the active site of ZIKV protease at a low docking energy (-7.8 Kcal/mol) via four hydrogen bonds with the protease residues TYR1130, SER1135, GLY1151, and ASP83. Doxycycline efficiently inhibited viral NS2B-NS3 protease at average human temperature (37 °C) and human temperature with a high fever during virus infection (40 °C). Interestingly, doxycycline showed a higher inhibitory effect at 40 °C (IC50 = 5.3 µM) compared to 37 °C (9.9 µM). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 µM of doxycycline. Treatment with 20 µM of doxycycline reduced the cytopathic effects (CPE), and the 40 µM of doxycycline almost eliminated the CPE of human skin cells. This study showed that doxycycline binds to the ZIKV protease and inhibits its catalytic activity at a low micro-molecular concentration range. Treatment of human skin fibroblast with doxycycline eliminated ZIKV infection and protected the cells against the cytopathic effects of the infection.
    Matched MeSH terms: Viral Nonstructural Proteins/antagonists & inhibitors*; Viral Nonstructural Proteins/metabolism; Viral Nonstructural Proteins/chemistry
  13. Kim JH, Chong CK, Sinniah M, Sinnadurai J, Song HO, Park H
    J Clin Virol, 2015 Apr;65:11-9.
    PMID: 25766980 DOI: 10.1016/j.jcv.2015.01.018
    BACKGROUND: Dengue is a mosquito-borne disease that causes a public health problem in tropical and subtropical countries. Current immunological diagnostics based on IgM and/or nonstructural protein 1 (NS1) antigen are limited for acute dengue infection due to low sensitivity and accuracy.
    OBJECTIVES: This study aimed to develop a one-step multiplex real-time RT-PCR assay showing higher sensitivity and accuracy than previous approaches.
    STUDY DESIGN: Serotype-specific primers and probes were designed through the multiple alignment of NS1 gene. The linearity and limit of detection (LOD) of the assay were determined. The assay was clinically validated with an evaluation panel that was immunologically tested by WHO and Malaysian specimens.
    RESULTS: The LOD of the assay was 3.0 log10 RNA copies for DENV-1, 2.0 for DENV-3, and 1.0 for DENV-2 and DENV-4. The assay showed 95.2% sensitivity (20/21) in an evaluation panel, whereas NS1 antigen- and anti-dengue IgM-based immunological assays exhibited 0% and 23.8-47.6% sensitivities, respectively. The assay showed 100% sensitivity both in NS1 antigen- and anti-dengue IgM-positive Malaysian specimens (26/26). The assay provided the information of viral loads and serotype with discrimination of heterotypic mixed infection.
    CONCLUSIONS: The assay could be clinically applied to early dengue diagnosis, especially during the first 5 days of illness and approximately 14 days after infection showing an anti-dengue IgM-positive response.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics*
  14. Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, et al.
    PLoS Negl Trop Dis, 2014 Oct;8(10):e3171.
    PMID: 25330157 DOI: 10.1371/journal.pntd.0003171
    Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%.
    Matched MeSH terms: Viral Nonstructural Proteins; Viral Nonstructural Proteins/immunology*
  15. Rothan HA, Mohamed Z, Paydar M, Rahman NA, Yusof R
    Arch Virol, 2014 Apr;159(4):711-8.
    PMID: 24142271 DOI: 10.1007/s00705-013-1880-7
    Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC50 value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC50, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC50) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.
    Matched MeSH terms: Viral Nonstructural Proteins/antagonists & inhibitors
  16. Osman O, Fong MY, Devi S
    PMID: 18567445
    A preliminary study of dengue infection in Brunei between 2005 and 2006 showed that dengue 2 was the predominant serotype. A total of five DEN-2 isolates were isolated and maintained in the mosquito cell-line, albopictus C6/36. The sequence spanning the envelope and non-structural protein 1 (E/NS1) junction (positions 2311 to 2550) of the isolates were determined and analysed at the amino acid and nucleotide levels. Alignment of the 240 nucleotide sequences among the five isolates showed changes occurring at 7 positions (2.9%) of the region. All but one nucleotide substitution (position 2319, amino acid 742 V --> F) were found at the 3rd position of the codons and were silent mutations. Amino acid homology ranged from 98% to 100%. Sequence divergence of the Brunei isolates varied from 5% to 6.6% compared with dengue-2 prototype New Guinea C strain. Comparison of the Brunei DEN-2 isolates with sixty-five other strains placed them in a cluster containing Indonesian strains isolated in 1973, 1978 and 2004 and Malaysian strains isolated in 1996, 1998 and 1999 in genotype group IV.
    Matched MeSH terms: Viral Nonstructural Proteins/genetics*
  17. AbuBakar S, Azmi A, Mohamed-Saad N, Shafee N, Chee HY
    Malays J Pathol, 1997 Jun;19(1):41-51.
    PMID: 10879241
    The present study was undertaken to investigate the antibody responses of dengue fever (DF) patients to specific dengue virus proteins. Partially purified dengue 2 New Guinea C (NGC) strain virus was used as antigen. Under the present experimental protocols, it was observed that almost all DF patients' sera had detectable presence of antibodies which recognize the dengue 2 envelope (E) protein. The convalescent-phase sera especially had significant detectable IgG, IgM and IgE against the protein. In addition, IgGs specific against the NS1 dimer and PrM were also detected. Antibody against the core (C) protein, however, was not detectable in any of the DF patients' sera. The substantial presence of IgG against the PrM in the convalescent-phase sera, and the presence of IgE specific for the E, reflect the potential importance of these antibody responses in the pathogenesis of dengue.
    Matched MeSH terms: Viral Nonstructural Proteins/immunology*
  18. Liew JWK, Selvarajoo S, Tan W, Ahmad Zaki R, Vythilingam I
    Infect Dis Poverty, 2019 Sep 03;8(1):71.
    PMID: 31477185 DOI: 10.1186/s40249-019-0584-y
    BACKGROUND: Dengue is a global disease, transmitted by the Aedes vectors. In 2018, there were 80 615 dengue cases with 147 deaths in Malaysia. Currently, the nationwide surveillance programs are dependent on Aedes larval surveys and notifications of lab-confirmed human infections. The existing, reactive programs appear to lack sensitivity and proactivity. More efficient dengue vector surveillance/control methods are needed.

    METHODS: A parallel, cluster, randomized controlled, interventional trial is being conducted for 18 months in Damansara Damai, Selangor, Malaysia, to determine the efficacy of using gravid oviposition sticky (GOS) trap and dengue non-structural 1 (NS1) antigen test for early surveillance of dengue among Aedes mosquitoes to reduce dengue outbreaks. Eight residential apartments were randomly assigned into intervention and control arms. GOS traps are set at the apartments to collect Aedes weekly, following which dengue NS1 antigen is detected in these mosquitoes. When a dengue-positive mosquito is detected, the community will be advised to execute vector search-and-destroy and protective measures. The primary outcome concerns the the percentage change in the (i) number of dengue cases and (ii) durations of dengue outbreaks. Whereas other outcome measures include the change in density threshold of Aedes and changes in dengue-related knowledge, attitude and practice among cluster inhabitants.

    DISCUSSION: This is a proactive and early dengue surveillance in the mosquito vector that does not rely on notification of dengue cases. Surveillance using the GOS traps should be able to efficiently provide sufficient coverage for multistorey dwellings where population per unit area is likely to be higher. Furthermore, trapping dengue-infected mosquitoes using the GOS trap, helps to halt the dengue transmission carried by the mosquito. It is envisaged that the results of this randomized controlled trial will provide a new proactive, cheap and targeted surveillance tool for the prevention and control of dengue outbreaks.

    TRIAL REGISTRATION: This is a parallel-cluster, randomized controlled, interventional trial, registered at ClinicalTrials.gov (ID: NCT03799237), on 8th January 2019 (retrospectively registered).

    Matched MeSH terms: Viral Nonstructural Proteins/analysis*
  19. Shalayel MH, Al-Mazaideh GM, Aladaileh SH, Al-Swailmi FK, Al-Thiabat MG
    Pak J Pharm Sci, 2020 Sep;33(5):2179-2186.
    PMID: 33824127
    Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.
    Matched MeSH terms: Viral Nonstructural Proteins/metabolism
  20. Liew JWK, Selvarajoo S, Phang WK, Mah Hassan M, Redzuan MS, Selva Kumar S, et al.
    Acta Trop, 2021 Apr;216:105829.
    PMID: 33465350 DOI: 10.1016/j.actatropica.2021.105829
    The aim of this study is to investigate the feasibility and outcomes of using Gravid Oviposition Sticky (GOS) trap and dengue NS1 antigen tests for indoor and outdoor dengue/Aedes surveillance in the field. A one-year community-based study was carried out at Sungai Buloh Hospital Quarters, Selangor, Malaysia. GOS traps were first placed outdoors in three apartment blocks (Anggerik, Bunga Raya and Mawar). Beginning 29th week of the study, indoor traps were set in two apartment units on every floor in Anggerik. All female Aedes mosquitoes caught were tested for the presence of dengue NS1 antigen. Dengue seroprevalence and knowledge, attitude and practices on dengue prevention of the community and their reception to the surveillance approach were also assessed. Dengue-positive mosquitoes were detected at least 1 week before a dengue onset. More mosquitoes were caught indoors than outdoors in block Anggerik, but the total number of mosquitoes caught in all 3 blocks were similar. There was a significant difference in distribution of Ae. aegypti and Ae. albopictus between the 3 blocks. 66.1% and 3.4% of the community were positive for dengue IgG and IgM, respectively. Most respondents think that this surveillance method is Good (89%) and support its use nationwide. Dengue case ratio in the study apartment blocks decreased from year 2018 to 2019. This study demonstrated the practicality of performing proactive dengue/Aedes surveillance inside apartment units using the GOS traps. This surveillance method can be performed with immediate result output in the field.
    Matched MeSH terms: Viral Nonstructural Proteins/analysis*
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