Displaying publications 1 - 20 of 55 in total

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  1. Malik FZ, Allaudin ZN, Loh HS, Nee TK, Hani H, Abdullah R
    BMC Complement Altern Med, 2016 May 23;16:139.
    PMID: 27216794 DOI: 10.1186/s12906-016-1120-2
    Duabanga grandiflora or known in Malaysia as Berembang Bukit, Megawasih, or Pedada Bukit, is a native plant of the Southeast Asian countries. In this study, the anti-viral properties of D. grandiflora were investigated.
    Matched MeSH terms: Virus Replication/drug effects
  2. Zandi K, Lani R, Wong PF, Teoh BT, Sam SS, Johari J, et al.
    Molecules, 2012;17(3):2437-45.
    PMID: 22374315 DOI: 10.3390/molecules17032437
    This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone) on DENV-2 infectivity in Vero cells. Virus adsorption and attachment and intracellular virus replication were investigated using a foci forming unit assay (FFUA) and quantitative RT-PCR, respectively. Addition of flavone (100 μg/mL) significantly increased the number of DENV-2 foci by 35.66% ± 1.52 and 49.66% ± 2.51 when added during and after virus adsorption to the Vero cells, respectively. The average foci size after 4 days of infection increased by 33% ± 2.11 and 89% ± 2.13. The DENV-2 specific RNA copy number in the flavone-treated infected cells increased by 6.41- and 23.1-fold when compared to the mock-treated infected cells. Flavone (100 μg/mL) did not promote or inhibit Vero cell proliferation. The CC₅₀ value of flavone against Vero cells was 446 µg/mL. These results suggest that flavone might enhance dengue virus replication by acting antagonistically towards flavonoids known to inhibit dengue virus replication.
    Matched MeSH terms: Virus Replication/drug effects*
  3. Mohd A, Zainal N, Tan KK, AbuBakar S
    Sci Rep, 2019 10 04;9(1):14336.
    PMID: 31586088 DOI: 10.1038/s41598-019-50674-3
    Zika virus (ZIKV) infection is a serious public health concern. ZIKV infection has been associated with increased occurrences of microcephaly among newborns and incidences of Guillain-Barré syndrome among adults. No specific therapeutics or vaccines are currently available to treat and protect against ZIKV infection. Here, a plant-secreted phytoalexin, resveratrol (RES), was investigated for its ability to inhibit ZIKV replication in vitro. Several RES treatment regimens were used. The ZIKV titers of mock- and RES-treated infected cell cultures were determined using the focus-forming assay and the Zika mRNA copy number as determined using qRT-PCR. Our results suggested that RES treatment reduced ZIKV titers in a dose-dependent manner. A reduction of >90% of virus titer and ZIKV mRNA copy number was achieved when infected cells were treated with 80 µM of RES post-infection. Pre-incubation of the virus with 80 µM RES showed >30% reduction in ZIKV titers and ZIKV mRNA copy number, implying potential direct virucidal effects of RES against the virus. The RES treatment reduced >70% virus titer in the anti-adsorption assay, suggesting the possibility that RES also interferes with ZIKV binding. However, there was no significant decrease in ZIKV titer when a short-period of RES treatment was applied to cells before ZIKV infection (pre-infection) and after the virus bound to the cells (virus internalization inhibition), implying that RES acts through its continuous presence in the cell cultures after virus infection. Overall, our results suggested that RES exhibited direct virucidal activity against ZIKV and possessed anti-ZIKV replication properties, highlighting the need for further exploration of RES as a potential antiviral molecule against ZIKV infection.
    Matched MeSH terms: Virus Replication/drug effects*
  4. Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S
    PMID: 23140177 DOI: 10.1186/1472-6882-12-214
    Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits.
    Matched MeSH terms: Virus Replication/drug effects
  5. Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S
    Virol J, 2011;8:560.
    PMID: 22201648 DOI: 10.1186/1743-422X-8-560
    Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for each compound.
    Matched MeSH terms: Virus Replication/drug effects*
  6. Zandi K, Lim TH, Rahim NA, Shu MH, Teoh BT, Sam SS, et al.
    BMC Complement Altern Med, 2013 Apr 29;13:91.
    PMID: 23627436 DOI: 10.1186/1472-6882-13-91
    BACKGROUND: Scutellaria baicalensis (S. baicalensis) is one of the traditional Chinese medicinal herbs that have been shown to possess many health benefits. In the present study, we evaluated the in vitro antiviral activity of aqueous extract of the roots of S. baicalensis against all the four dengue virus (DENV) serotypes.

    METHODS: Aqueous extract of S. baicalensis was prepared by microwave energy steam evaporation method (MEGHE™), and the anti-dengue virus replication activity was evaluated using the foci forming unit reduction assay (FFURA) in Vero cells. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the actual dengue virus RNA copy number. The presence of baicalein, a flavonoid known to inhibit dengue virus replication was determined by mass spectrometry.

    RESULTS: The IC(50) values for the S. baicalensis extract on Vero cells following DENV adsorption ranged from 86.59 to 95.19 μg/mL for the different DENV serotypes. The IC(50) values decreased to 56.02 to 77.41 μg/mL when cells were treated with the extract at the time of virus adsorption for the different DENV serotypes. The extract showed potent direct virucidal activity against extracellular infectious virus particles with IC(50) that ranged from 74.33 to 95.83 μg/mL for all DENV serotypes. Weak prophylactic effects with IC(50) values that ranged from 269.9 to 369.8 μg/mL were noticed when the cells were pre-treated 2 hours prior to virus inoculation. The concentration of baicalein in the S. baicalensis extract was ~1% (1.03 μg/gm dried extract).

    CONCLUSIONS: Our study demonstrates the in vitro anti-dengue virus replication property of S. baicalensis against all the four DENV serotypes investigated. The extract reduced DENV infectivity and replication in Vero cells. The extract was rich in baicalein, and could be considered for potential development of anti-DENV therapeutics.

    Matched MeSH terms: Virus Replication/drug effects*
  7. Panda S, Banik U, Adhikary AK
    Infect Genet Evol, 2020 11;85:104439.
    PMID: 32585339 DOI: 10.1016/j.meegid.2020.104439
    Human adenovirus type 3 (HAdV-3) encompasses 15-87% of all adenoviral respiratory infections. The significant morbidity and mortality, especially among the neonates and immunosuppressed patients, demand the need for a vaccine or a targeted antiviral against this type. However, due to the existence of multiple hexon variants (3Hv-1 to 3Hv-25), the selection of vaccine strains of HAdV-3 is challenging. This study was designed to evaluate HAdV-3 hexon variants for the selection of potential vaccine candidates and the use of hexon gene as a target for designing siRNA that can be used as a therapy. Based on the data of worldwide distribution, duration of circulation, co-circulation and their percentage among all the variants, 3Hv-1 to 3Hv-4 were categorized as the major hexon variants. Phylogenetic analysis and the percentage of homology in the hypervariable regions followed by multi-sequence alignment, zPicture analysis and restriction enzyme analysis were carried out. In the phylogram, the variants were arranged in different clusters. The HVR encoding regions of hexon of 3Hv-1 to 3Hv-4 showed 16 point mutations resulting in 12 amino acids substitutions. The homology in HVRs was 81.81-100%. Therefore, the major hexon variants are substantially different from each other which justifies their inclusion as the potential vaccine candidates. Interestingly, despite the significant differences in the DNA sequence, there were many conserved areas in the HVRs, and we have designed functional siRNAs form those locations. We have also designed immunogenic vaccine peptide epitopes from the hexon protein using bioinformatics prediction tool. We hope that our developed siRNAs and immunogenic vaccine peptide epitopes could be used in the future development of siRNA-based therapy and designing a vaccine against HAdV-3.
    Matched MeSH terms: Virus Replication/drug effects
  8. Jasamai M, Simons C, Balzarini J
    PMID: 20589572 DOI: 10.1080/15257771003781634
    Acyclic nucleosides have been of considerable interest since the approval of aciclovir by the FDA to be used as an antiviral agent in the 1990s. The acyclic moieties and the bases used in the experiment were either available commercially or synthesized using literature methods. Vorbruggen coupling method was utilized involving reaction of persilylated heterocyclic bases with the appropriate acyclic moiety in the presence of a Lewis acid catalyst. A series of novel 6-azapyrimidine acyclic oxosugar nucleosides was successfully synthesized with a promising yield (more than 50%). An efficient method of protection and deprotection was also investigated.
    Matched MeSH terms: Virus Replication/drug effects
  9. Tan CW, Lai JK, Sam IC, Chan YF
    J Biomed Sci, 2014;21:14.
    PMID: 24521134 DOI: 10.1186/1423-0127-21-14
    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.
    Matched MeSH terms: Virus Replication/drug effects
  10. Tan CW, Sam IC, Chong WL, Lee VS, Chan YF
    Antiviral Res, 2017 07;143:186-194.
    PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017
    Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
    Matched MeSH terms: Virus Replication/drug effects
  11. Chen YF, Chong CL, Wu YC, Wang YL, Tsai KN, Kuo TM, et al.
    PLoS One, 2015;10(6):e0131743.
    PMID: 26121644 DOI: 10.1371/journal.pone.0131743
    Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s) through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1) in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα); such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy.
    Matched MeSH terms: Virus Replication/drug effects*
  12. Dighe SN, Ekwudu O, Dua K, Chellappan DK, Katavic PL, Collet TA
    Eur J Med Chem, 2019 Aug 15;176:431-455.
    PMID: 31128447 DOI: 10.1016/j.ejmech.2019.05.010
    Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
    Matched MeSH terms: Virus Replication/drug effects
  13. Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC, et al.
    J Ethnopharmacol, 2008 Oct 30;120(1):108-11.
    PMID: 18762235 DOI: 10.1016/j.jep.2008.07.048
    Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by the SARS coronavirus (SARS-CoV). The development of new antiviral agents for SARS-CoV is an important issue. We tried to find potential resource from Traditional Chinese medicine (TCM) for development of new drugs against SARS-CoV.
    Matched MeSH terms: Virus Replication/drug effects*
  14. Wong WY, Loh SW, Ng WL, Tan MC, Yeo KS, Looi CY, et al.
    Sci Rep, 2015;5:8672.
    PMID: 25728279 DOI: 10.1038/srep08672
    Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
    Matched MeSH terms: Virus Replication/drug effects
  15. Tan MC, Wong WY, Ng WL, Yeo KS, Mohidin TB, Lim YY, et al.
    PLoS One, 2017;12(1):e0170352.
    PMID: 28114392 DOI: 10.1371/journal.pone.0170352
    Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation. We reported that pre-treating cells with 526A protects cells from IAV infection. Furthermore, 526A inhibits IAV replication by inhibiting the expression of IAV genes. Interestingly, 526A suppresses the activation of IRF3 and STAT1 in host cells and thus represses the production of type I interferon response and cytokines in IAV-infected cells. Importantly, 526A also partially blocks the activation of RIG-I pathway. Taken together, these results suggest that 526A may be a potential anti-influenza A virus agent.
    Matched MeSH terms: Virus Replication/drug effects
  16. Rothan HA, Zhong Y, Sanborn MA, Teoh TC, Ruan J, Yusof R, et al.
    Antiviral Res, 2019 11;171:104590.
    PMID: 31421166 DOI: 10.1016/j.antiviral.2019.104590
    Two major flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), cause severe health and economic burdens worldwide. Recently, genome-wide screenings have uncovered the importance of regulators of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway for flavivirus replication in host cells. Here we report the identification of the compound Bardoxolone methyl (CDDO-me) as a potent inhibitor of the Hrd1 ubiquitin ligase-mediated ERAD, which possesses a broad-spectrum activity against both DENV and ZIKV. Cellular thermal shift assay (CETSA) suggested that CDDO-me binds to grp94, a key component of the Hrd1 pathway, at a low nanomolar concentration, whereas interaction was not detected with its paralog Hsp90. CDDO-me and the grp94 inhibitor PU-WS13 substantially suppressed DENV2 replication and the cytopathic effects caused by DENV and ZIKV infection. The antiviral activities of both compounds were demonstrated for all four DENV serotypes and four ZIKV strains in multiple human cell lines. This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
    Matched MeSH terms: Virus Replication/drug effects
  17. Lim SK, Othman R, Yusof R, Heh CH
    Chem Biol Drug Des, 2021 01;97(1):28-40.
    PMID: 32657543 DOI: 10.1111/cbdd.13756
    Structure-based virtual screening (SBVS) has served as a popular strategy for rational drug discovery. In this study, we aimed to discover novel benzopyran-based inhibitors that targeted the NS3 enzymes (NS3/4A protease and NS3 helicase) of HCV G3 using a combination of in silico and in vitro approaches. With the aid of SBVS, six novel compounds were discovered to inhibit HCV G3 NS3/4A protease and two phytochemicals (ellagic acid and myricetin) were identified as dual-target inhibitors that inhibited both NS3/4A protease and NS3 helicase in vitro (IC50  = 40.37 ± 5.47 nm and 6.58 ± 0.99 µm, respectively). Inhibitory activities against the replication of HCV G3 replicons were further assessed in a cell-based system with four compounds showed dose-dependent inhibition. Compound P8 was determined to be the most potent compound from the cell-based assay with an EC50 of 19.05 µm. The dual-target inhibitor, ellagic acid, was determined as the second most potent (EC50  = 32.37 µm) and the most selective in its inhibitory activity against the replication of HCV replicons, without severely affecting the viability of the host cells (selectivity index > 6.18).
    Matched MeSH terms: Virus Replication/drug effects
  18. Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
    Matched MeSH terms: Virus Replication/drug effects
  19. Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al.
    Int J Mol Med, 2014 Jul;34(1):61-73.
    PMID: 24788303 DOI: 10.3892/ijmm.2014.1761
    Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.
    Matched MeSH terms: Virus Replication/drug effects*
  20. Low ZY, Yip AJW, Lal SK
    Biochim Biophys Acta Mol Basis Dis, 2022 Feb 01;1868(2):166294.
    PMID: 34687900 DOI: 10.1016/j.bbadis.2021.166294
    Ivermectin (IVM) is an FDA approved macrocyclic lactone compound traditionally used to treat parasitic infestations and has shown to have antiviral potential from previous in-vitro studies. Currently, IVM is commercially available as a veterinary drug but have also been applied in humans to treat onchocerciasis (river blindness - a parasitic worm infection) and strongyloidiasis (a roundworm/nematode infection). In light of the recent pandemic, the repurposing of IVM to combat SARS-CoV-2 has acquired significant attention. Recently, IVM has been proven effective in numerous in-silico and molecular biology experiments against the infection in mammalian cells and human cohort studies. One promising study had reported a marked reduction of 93% of released virion and 99.98% unreleased virion levels upon administration of IVM to Vero-hSLAM cells. IVM's mode of action centres around the inhibition of the cytoplasmic-nuclear shuttling of viral proteins by disrupting the Importin heterodimer complex (IMPα/β1) and downregulating STAT3, thereby effectively reducing the cytokine storm. Furthermore, the ability of IVM to block the active sites of viral 3CLpro and S protein, disrupts important machinery such as viral replication and attachment. This review compiles all the molecular evidence to date, in review of the antiviral characteristics exhibited by IVM. Thereafter, we discuss IVM's mechanism and highlight the clinical advantages that could potentially contribute towards disabling the viral replication of SARS-CoV-2. In summary, the collective review of recent efforts suggests that IVM has a prophylactic effect and would be a strong candidate for clinical trials to treat SARS-CoV-2.
    Matched MeSH terms: Virus Replication/drug effects*
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