Displaying publications 181 - 200 of 207 in total

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  1. Fulltext Novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus -1: an in vitro study on virally infected Vero and MRC-5 cell lines
    Hafidh RR, Abdulamir AS, Abu Bakar F, Sekawi Z, Jahansheri F, Jalilian FA
    BMC Complement Altern Med, 2015;15:179.
    PMID: 26062546 DOI: 10.1186/s12906-015-0688-2
    New sources for discovering novel antiviral agents are desperately needed. The current antiviral products are both expensive and not very effective.
    Matched MeSH terms: Cercopithecus aethiops
  2. The application of naked DNA plasmid (DrZP3) and recombinant adenovirus (Ad-rZP3) in rat animal model to determine comparative efficacy of ZP3-Immunocontraceptive vaccines
    Mohd-Lila MA, Yee LK, Cen LS, Bala JA, Balakrishnan KN, Allaudin ZN, et al.
    Microb Pathog, 2019 Sep;134:103572.
    PMID: 31163251 DOI: 10.1016/j.micpath.2019.103572
    The common physical and chemical methods for controlling rat pest are less than satisfactory and inhumane. Immunocontraception approach has been considered more humane and it can be accomplished by inducing the relevant host immune response that block further development of reproductive gametes. ZP3 proteins are known to play very important role during sperm-ovum fertilization. It is a self-antigen and only localized in female ovaries. Therefore, an immunization with ZP3 protein elsewhere will induce a generalize host immune response against ZP3 protein. This study employed rat ZP3 (rZP3) gene prepared from its cDNA of Rattus rattus diardii. It was delivered and expressed in vivo by naked plamid DNA (DrZP3) or recombinant ZP3-Adenovirus (Ad-rZP3). Expression studies in vitro with DrZP3 or Ad-ZP3 showed rZP3 proteins were successfully expressed in Vero cells. Hyperimmune serum against rZP3 that were prepared by immunizing several rats with purified rZP3-pichia yeast fusion protein showed it blocked sperms from binding DrZP3-transfected Vero cells. Female Sprague Dawley rats immunized with DrZP3 demonstrated a long-term effect for significant reduction of fertility up to 92.6%. Ovaries from rats immunized with DrZP3 were severely atrophied with disappearance of primordial follicles from ovarian cortex with an increased in the amount of oocyte-free cell clusters. Female rats immunized with Ad-rZP3 demonstrated 27% reduction of fertility. The infertility induced by Ad-rZP3 is comparatively low and ineffective. This could be due to a strong host immune response that suppresses the recombinant virus itself resulted in minimum rZP3 protein presentation to the host immune system. As a result, low antibody titers produced against rZP3 is insufficient to block oocytes from maturity and fertilization. Therefore, immunization with DrZP3 for immunocontraception is more effective than Ad-rZP3 recombinant adenovirus. It is proposed to explore further on the use of adenovirus or other alternative viruses to deliver ZP3 protein and for the development of enhanced expression of rZP3 in target host.
    Matched MeSH terms: Cercopithecus aethiops
  3. Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery
    Yuan X, Amarnath Praphakar R, Munusamy MA, Alarfaj AA, Suresh Kumar S, Rajan M
    Carbohydr Polym, 2019 Feb 15;206:1-10.
    PMID: 30553301 DOI: 10.1016/j.carbpol.2018.10.098
    Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.
    Matched MeSH terms: Cercopithecus aethiops
  4. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins
    Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al.
    Nature, 2020 07;583(7815):286-289.
    PMID: 32380510 DOI: 10.1038/s41586-020-2313-x
    The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
    Matched MeSH terms: Cercopithecus aethiops
  5. Fulltext Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study
    Hariono M, Rollando R, Karamoy J, Hariyono P, Atmono M, Djohan M, et al.
    Molecules, 2020 Oct 14;25(20).
    PMID: 33066411 DOI: 10.3390/molecules25204691
    Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a step-by-step in vitro screening against MMP9 was performed from its crude extract, partitions until fractions using FRET-based assay. The partitions were obtained by performing liquid-liquid extraction on the methanol extract using n-hexane, ethylacetate, n-butanol, and water representing nonpolar to polar solvents. The fractions were made from the selected partition, which demonstrated the best inhibition percentage toward MMP9, using column chromatography. Of the 200 compounds screened, 20 compounds that scored the binding affinity -11.2 to -8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. Six of the eight crude extracts demonstrated inhibition toward MMP9 with the IC50 24 to 823 µg/mL. The partitions (1 mg/mL) of Ageratum conyzoides aerial parts and Ixora coccinea leaves showed inhibition 94% and 96%, whereas their fractions showed IC50 43 and 116 µg/mL, respectively toward MMP9. Using MTT assay, the crude extract of Ageratum exhibited IC50 22 and 229 µg/mL against 4T1 and T47D cell proliferations, respectively with a high safety index concluding its potential anti-breast cancer from herbal.
    Matched MeSH terms: Cercopithecus aethiops
  6. Tembusu-like flavivirus (Perak virus) as the cause of neurological disease outbreaks in young Pekin ducks
    Homonnay ZG, Kovács EW, Bányai K, Albert M, Fehér E, Mató T, et al.
    Avian Pathol, 2014;43(6):552-60.
    PMID: 25299764 DOI: 10.1080/03079457.2014.973832
    A neurological disease of young Pekin ducks characterized by ataxia, lameness, and paralysis was observed at several duck farms in Malaysia in 2012. Gross pathological lesions were absent or inconsistent in most of the cases, but severe and consistent microscopic lesions were found in the brain and spinal cord, characterized by non-purulent panencephalomyelitis. Several virus isolates were obtained in embryonated duck eggs and in cell cultures (Vero and DF-1) inoculated with the brain homogenates of affected ducks. After exclusion of other viruses, the isolates were identified as a flavivirus by flavivirus-specific reverse transcription-polymerase chain reaction (RT-PCR) assays. Inoculation of 2-week-old Pekin ducks with a flavivirus isolate by the subcutaneous or intramuscular route resulted in typical clinical signs and histological lesions in the brain and spinal cord. The inoculated virus was detected by RT-PCR from organ samples of ducks with clinical signs and histological lesions. With a few days delay, the disease was also observed among co-mingled contact control birds. Phylogenetic analysis of NS5 and E gene sequences proved that the isolates were representatives of a novel phylogenetic group within clade XI (Ntaya virus group) of the Flavivirus genus. This Malaysian Duck Tembusu Virus (DTMUV), named Perak virus, has moderate genomic RNA sequence similarity to a related DTMUV identified in China. In our experiment the Malaysian strain of DTMUV could be transmitted in the absence of mosquito vectors. These findings may have implications for the control and prevention of this emerging group of flaviviruses.
    Matched MeSH terms: Cercopithecus aethiops
  7. Fulltext Antitrypanosomal screening and cytotoxic effects of selected medicinal plants
    Dyary HO, Arifah AK, Sharma RS, Rasedee A, Mohd-Aspollah MS, Zakaria ZA, et al.
    Trop Biomed, 2014 Mar;31(1):89-96.
    PMID: 24862048 MyJurnal
    Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 μg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 μg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.
    Matched MeSH terms: Cercopithecus aethiops
  8. Fulltext Comparative genetic analysis of VP4, VP1 and 3D gene regions of enterovirus 71 and coxsackievirus A16 circulating in Malaysia between 1997-2008
    Chan YF, Wee KL, Chiam CW, Khor CS, Chan SY, Amalina W MZ, et al.
    Trop Biomed, 2012 Sep;29(3):451-66.
    PMID: 23018509 MyJurnal
    Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997- 2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.
    Matched MeSH terms: Cercopithecus aethiops
  9. Fulltext In Silico, Cytotoxic and Antioxidant Potential of Novel Ester, 3-hydroxyoctyl -5- trans-docosenoate Isolated from Anchusa arvensis (L.) M.Bieb. Against HepG-2 Cancer Cells
    Hussain S, Ullah F, Ayaz M, Ali Shah SA, Ali Shah AU, Shah SM, et al.
    Drug Des Devel Ther, 2019;13:4195-4205.
    PMID: 31849451 DOI: 10.2147/DDDT.S228971
    Background: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. Anchusa arvensis (A. anchusa) (L.) M.Bieb. contains many biologically active compounds.

    Methods: In the current study, new ester 3-hydroxyoctyl -5- trans-docosenoate (compound-1) was isolated from the chloroform soluble fraction of A. anchusa using column chromatography. Using MTT assay, the anticancer effect of the compound was determined in human hepatocellular carcinoma cells (HepG-2) compared with normal epithelial cell line (Vero). DPPH and ABTS radical scavenging assays were performed to assess the antioxidant potential. The Molecular Operating Environment (MOE-2016) tool was used against tyrosine kinase.

    Results: The structure of the compound was elucidated based on IR, EI, and NMR spectroscopy technique. It exhibited a considerable cytotoxic effect against HepG-2 cell lines with IC50 value of 6.50 ± 0.70 µg/mL in comparison to positive control (doxorubicin) which showed IC50 value of 1.3±0.21 µg/mL. The compound did not show a cytotoxic effect against normal epithelial cell line (Vero). The compound also exhibited significant DPHH scavenging ability with IC50 value of 12 ± 0.80 µg/mL, whereas ascorbic acid, used as positive control, demonstrated activity with IC50 = 05 ± 0.15 µg/mL. Similarly, it showed ABTS radical scavenging ability (IC50 = 130 ± 0.20 µg/mL) compared with the value obtained for ascorbic acid (06 ± 0.85 µg/mL). In docking studies using MOE-2016 tool, it was observed that compound-1 was highly bound to tyrosine kinase by having two hydrogen bonds at the hinge region. This good bonding network by the compound might be one of the reasons for showing significant activity against this enzyme.

    Conclusion: Our findings led to the isolation of a new compound from A. anchusa which has significant cytotoxic activity against HepG-2 cell lines with marked antioxidant potential.

    Matched MeSH terms: Cercopithecus aethiops
  10. Fulltext Mast cell stabilizing effect of a geranyl acetophenone in dengue virus infection using in vitro model of DENV3-induced RBL-2H3 cells
    Tan JW, Wan Zahidi NF, Kow ASF, Soo KM, Shaari K, Israf DA, et al.
    Biosci Rep, 2019 06 28;39(6).
    PMID: 31110077 DOI: 10.1042/BSR20181273
    Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10-2 and 0.8 × 10-2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.
    Matched MeSH terms: Cercopithecus aethiops
  11. Improved protection from velogenic Newcastle disease virus challenge following multiple immunizations with plasmid DNA encoding for F and HN genes
    Loke CF, Omar AR, Raha AR, Yusoff K
    Vet Immunol Immunopathol, 2005 Jul 15;106(3-4):259-67.
    PMID: 15963824
    Specific-pathogen free (SPF) chickens were inoculated with the plasmid constructs encoding the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of Newcastle disease virus (NDV), either individually or in combination and challenged with velogenic NDV. The antibody level against NDV was measured using commercial enzyme linked immunosorbent assay (ELISA). In the first immunization regimen, SPF chickens inoculated twice with NDV-F or NDV-HN constructs elicited antibody responses 1 week after the second injection. However, the levels of the antibody were low and did not confer significant protection from the lethal challenge. In addition, administration of the plasmid constructs with Freund's adjuvant did not improve the level of protection. In the second immunization regimen, chickens inoculated twice with the plasmid constructs emulsified with Freund's adjuvant induced significant antibody titers after the third injection. Three out of nine (33.3%) chickens vaccinated with pEGFP-HN, five of ten (50.0%) chickens vaccinated with pEGFP-F and nine of ten (90.0%) chickens vaccinated with combined pEGFP-F and pEGFP-HN were protected from the challenge. No significant differences in the levels of protection were observed when the chickens were vaccinated with linearized pEGFP-F. The results suggested that more than two injections with both F and HN encoding plasmid DNA were required to induce higher level of antibodies for protection against velogenic NDV in chickens.
    Matched MeSH terms: Cercopithecus aethiops
  12. Biological evaluation the 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones as potential dual α-glucosidase and α-amylase inhibitors with antioxidant properties
    Mphahlele MJ, Magwaza NM, Malindisa ST, Choong YS
    Chem Biol Drug Des, 2021 08;98(2):234-247.
    PMID: 34013660 DOI: 10.1111/cbdd.13893
    The 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones (azaborininone) were synthesized as analogues of the 2-arylquinazoline-4-ones and screened through enzymatic assay in vitro for inhibitory effect against α-glucosidase and α-amylase activities. These azaborininones exhibited moderate to good inhibitory effect against these enzymes compared to acarbose used as a reference standard. The results are supported by the enzyme-ligand interactions through kinetics (in vitro) and molecular docking (in silico) studies. The test compounds also exhibited significant antioxidant activity through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. These azaborininone derivatives exhibited no effect on the viability of the human lung cancer (A549) cell line after 24 hr and were also not toxic towards the Vero cells.
    Matched MeSH terms: Cercopithecus aethiops
  13. In vitro and in vivo toxicity assessment of alginate/eudragit S 100-enclosed chitosan-calcium phosphate-loaded iron saturated bovine lactoferrin nanocapsules (Fe-bLf NCs)
    Leng KM, Vijayarathna S, Jothy SL, Sasidharan S, Kanwar JR
    Biomed Pharmacother, 2018 Jan;97:26-37.
    PMID: 29080455 DOI: 10.1016/j.biopha.2017.10.121
    Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15μg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536μg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100μg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000μg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.
    Matched MeSH terms: Cercopithecus aethiops
  14. Fulltext Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
    Abdul Ahmad SA, Palanisamy UD, Tejo BA, Chew MF, Tham HW, Syed Hassan S
    Virol J, 2017 11 21;14(1):229.
    PMID: 29162124 DOI: 10.1186/s12985-017-0895-1
    BACKGROUND: The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated.

    METHODS: Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays'. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay.

    RESULTS: Cytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC50 of 1.75 μM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin's interaction with rE-DIII with high affinity.

    CONCLUSIONS: Geraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for early phase dengue viral infection.

    Matched MeSH terms: Cercopithecus aethiops
  15. Fulltext Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses
    Zandi K, Bassit L, Amblard F, Cox BD, Hassandarvish P, Moghaddam E, et al.
    Antimicrob Agents Chemother, 2019 Jul;63(7).
    PMID: 31061163 DOI: 10.1128/AAC.00397-19
    Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.
    Matched MeSH terms: Cercopithecus aethiops
  16. Design and validation of small interfering RNA on respiratory syncytial virus M2-2 gene: A potential approach in RNA interference on viral replication
    Chin VK, Atika Aziz NA, Hudu SA, Harmal NS, Syahrilnizam A, Jalilian FA, et al.
    J Virol Methods, 2016 10;236:117-125.
    PMID: 27432115 DOI: 10.1016/j.jviromet.2016.07.012
    Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants and young children globally and is a significant pathogen of the elderly and immunocompromised. The M2-2 protein of respiratory syncytial virus (RSV) is particularly important in regulation of viral RNA transcription and replication that could be a potential anti-viral candidate against RSV infection. In this study, we designed and validated siRNAs that specifically target the RSV M2-2 gene. Four siRNAs targeting different regions of the M2-2 gene were designed using web tool. In-vitro evaluation of silencing effect was performed by using RSV infected Vero cell line. Viral M2-2 linked GFP recombinant plasmid was co-transfected with non-targeted siRNA, Pooled siRNA, siRNA 1, siRNA 2, siRNA 3 and siRNA 4 using synthetic cationic polymer. The silencing effect of M2-2 gene at the protein level was measured both qualitatively and quantitatively by using fluorescence microscopy and flow cytometry. Meanwhile, the silencing effect at the mRNA level was assessed by using RT-qPCR. This study showed that all four designed siRNAs can effectively and efficiently silence M2-2 gene. siRNA 2 showed the highest (98%) silencing effect on protein level and siRNA 4 with 83.1% at the mRNA level. The viral assay showed no significant cytopathic effects observed after 6days post-infection with siRNAs. In conclusion, this study showed the effectiveness of siRNA in silencing M2-2 gene both at the protein and mRNA level which could potentially be used as a novel therapeutic agent in the treatment of RSV infection. However, further study is warranted to investigate the silencing effect of M2-2 protein and inhibition of RSV infection.
    Matched MeSH terms: Cercopithecus aethiops
  17. The relationships between West Nile and Kunjin viruses
    Scherret JH, Poidinger M, Mackenzie JS, Broom AK, Deubel V, Lipkin WI, et al.
    Emerg Infect Dis, 2001 Jul-Aug;7(4):697-705.
    PMID: 11585535
    Until recently, West Nile (WN) and Kunjin (KUN) viruses were classified as distinct types in the Flavivirus genus. However, genetic and antigenic studies on isolates of these two viruses indicate that the relationship between them is more complex. To better define this relationship, we performed sequence analyses on 32 isolates of KUN virus and 28 isolates of WN virus from different geographic areas, including a WN isolate from the recent outbreak in New York. Sequence comparisons showed that the KUN virus isolates from Australia were tightly grouped but that the WN virus isolates exhibited substantial divergence and could be differentiated into four distinct groups. KUN virus isolates from Australia were antigenically homologous and distinct from the WN isolates and a Malaysian KUN virus. Our results suggest that KUN and WN viruses comprise a group of closely related viruses that can be differentiated into subgroups on the basis of genetic and antigenic analyses.
    Matched MeSH terms: Cercopithecus aethiops
  18. Isolation of Waddlia malaysiensis, a novel intracellular bacterium, from fruit bat (Eonycteris spelaea)
    Chua PK, Corkill JE, Hooi PS, Cheng SC, Winstanley C, Hart CA
    Emerg Infect Dis, 2005 Feb;11(2):271-7.
    PMID: 15752446
    An obligate intracellular bacterium was isolated from urine samples from 7 (3.5%) of 202 fruit bats (Eonycteris spelaea) in peninsular Malaysia. The bacterium produced large membrane-bound inclusions in human, simian, and rodent cell lines, including epithelial, fibroblastlike, and lymphoid cells. Thin-section electron microscopy showed reticulate bodies dividing by binary fission and elementary bodies in the inclusions; mitochondria surrounded the inclusions. The inclusions were positive for periodic acid-Schiff stain but could not be stained by fluorescein-labeled anti-Chlamydia trachomatis major outer membrane protein monoclonal antibody. The bacterium was resistant to penicillin and streptomycin (MICs > 256 mg/L) but susceptible to tetracycline (MIC = 0.25 mg/L) and chloramphenicol (MIC = 0.5 mg/L). Sequence analysis of the 16SrRNA gene indicated that it was most closely related to 2 isolates of Waddlia chondrophila (94% and 96% identity). The 16S and 23S rRNA gene signatures were only 91% identical. We propose this novel bacterium be called W. malaysiensis.
    Matched MeSH terms: Cercopithecus aethiops
  19. Fulltext Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum)
    Namvar F, Mohamad R, Baharara J, Zafar-Balanejad S, Fargahi F, Rahman HS
    Biomed Res Int, 2013;2013:604787.
    PMID: 24078922 DOI: 10.1155/2013/604787
    In the present study, we evaluated the effect of brown seaweeds Sargassum muticum methanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines proliferation. This algae extract was also evaluated for reducing activity and total polyphenol content. The MTT assay results indicated that the extracts were cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50 of 22 μg/ml for MCF-7 and 55 μg/ml for MDA-MB-231 cell lines. The percentages of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the concentration of the SMME. The antiproliferative efficacy of this algal extract was positively correlated with the total polyphenol contents, suggesting a causal link related to extract content of phenolic acids. Cell cycle analysis showed a significant increase in the accumulation of SMME-treated cells at sub-G1 phase, indicating the induction of apoptosis by SMME. Further apoptosis induction was confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into fertilized chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). Our results imply a new insight on the novel function of Sargassum muticum polyphenol-rich seaweed in cancer research by induction of apoptosis, antioxidant, and antiangiogenesis effects.
    Matched MeSH terms: Cercopithecus aethiops
  20. Fulltext Serotype-specific host responses in rhesus macaques after primary dengue challenge
    Hickey AC, Koster JA, Thalmann CM, Hardcastle K, Tio PH, Cardosa MJ, et al.
    Am J Trop Med Hyg, 2013 Dec;89(6):1043-57.
    PMID: 24062475 DOI: 10.4269/ajtmh.13-0145
    Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
    Matched MeSH terms: Cercopithecus aethiops
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